{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:25:29Z","timestamp":1785421529777,"version":"3.56.0"},"reference-count":199,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01GM130927"],"award-info":[{"award-number":["R01GM130927"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>A long-standing goal of amyloid research has been to characterize the structural basis of the rate-determining nucleating event. However, the ephemeral nature of nucleation has made this goal unachievable with existing biochemistry, structural biology, and computational approaches. Here, we addressed that limitation for polyglutamine (polyQ), a polypeptide sequence that causes Huntington\u2019s and other amyloid-associated neurodegenerative diseases when its length exceeds a characteristic threshold. To identify essential features of the polyQ amyloid nucleus, we used a direct intracellular reporter of self-association to quantify frequencies of amyloid appearance as a function of concentration, conformational templates, and rational polyQ sequence permutations. We found that nucleation of pathologically expanded polyQ involves segments of three glutamine (Q) residues at every other position. We demonstrate using molecular simulations that this pattern encodes a four-stranded steric zipper with interdigitated Q side chains. Once formed, the zipper poisoned its own growth by engaging naive polypeptides on orthogonal faces, in a fashion characteristic of polymer crystals with intramolecular nuclei. We further show that self-poisoning can be exploited to block amyloid formation, by genetically oligomerizing polyQ prior to nucleation. By uncovering the physical nature of the rate-limiting event for polyQ aggregation in cells, our findings elucidate the molecular etiology of polyQ diseases.<\/jats:p>","DOI":"10.7554\/elife.86939","type":"journal-article","created":{"date-parts":[[2023,6,13]],"date-time":"2023-06-13T08:18:35Z","timestamp":1686644315000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.86939","source":"Crossref","is-referenced-by-count":8,"title":["Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal"],"prefix":"10.7554","volume":"12","author":[{"given":"Tej","family":"Kandola","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]},{"id":[{"id":"https:\/\/ror.org\/05mzfcs16","id-type":"ROR","asserted-by":"publisher"}],"name":"The Open University","place":["Milton Keynes, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0778-2474","authenticated-orcid":true,"given":"Shriram","family":"Venkatesan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04tj63d06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physics, North Carolina State University","place":["Raleigh, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooklyn T","family":"Lerbakken","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Von Schulze","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian F","family":"Blanck","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzheng","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]},{"id":[{"id":"https:\/\/ror.org\/036c9yv20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Molecular Biology, University of Kansas Medical Center","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3077-4990","authenticated-orcid":true,"given":"Jay R","family":"Unruh","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Berry","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4970-6269","authenticated-orcid":true,"given":"Jeffrey J","family":"Lange","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C","family":"Box","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Cook","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celeste","family":"Sagui","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04tj63d06","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physics, North Carolina State University","place":["Raleigh, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6592-1471","authenticated-orcid":true,"given":"Randal","family":"Halfmann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bgfm609","id-type":"ROR","asserted-by":"publisher"}],"name":"Stowers Institute for Medical Research","place":["Kansas City, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1021\/acs.biochem.6b00936","article-title":"Proteins containing expanded polyglutamine tracts and neurodegenerative disease","volume":"56","author":"Adegbuyiro","year":"2017","journal-title":"Biochemistry"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201900489","article-title":"The huntingtin inclusion is a dynamic phase-separated compartment","volume":"2","author":"Aktar","year":"2019","journal-title":"Life Science Alliance"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"15185","DOI":"10.1074\/jbc.M802071200","article-title":"Appearance and propagation of polyglutamine-based amyloids in yeast: tyrosine residues enable polymer fragmentation","volume":"283","author":"Alexandrov","year":"2008","journal-title":"The Journal of Biological Chemistry"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046458","article-title":"The effects of amino acid composition of glutamine-rich domains on amyloid formation and fragmentation","volume":"7","author":"Alexandrov","year":"2012","journal-title":"PLOS ONE"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1021\/acs.biochem.9b00689","article-title":"Nucleation Inhibition of Huntingtin Protein (htt) by Polyproline PPII Helices: A Potential Interaction with the N-Terminal \u03b1-Helical Region of Htt","volume":"59","author":"Arndt","year":"2020","journal-title":"Biochemistry"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/nature02998","article-title":"Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death","volume":"431","author":"Arrasate","year":"2004","journal-title":"Nature"},{"key":"bib7","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000222","article-title":"A generic mechanism of emergence of amyloid protofilaments from disordered oligomeric aggregates","volume":"4","author":"Auer","year":"2008","journal-title":"PLOS Computational Biology"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"1595","DOI":"10.1016\/j.csbj.2021.02.014","article-title":"Dissecting the role of glutamine in seeding peptide aggregation","volume":"19","author":"Barrera","year":"2021","journal-title":"Computational and Structural Biotechnology Journal"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"15400","DOI":"10.1073\/pnas.0501651102","article-title":"polyglutamine aggregation nucleation: thermodynamics of a highly unfavorable protein folding reaction","volume":"102","author":"Bhattacharyya","year":"2005","journal-title":"PNAS"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"4722","DOI":"10.1016\/j.jmb.2020.06.021","article-title":"Protofilament structure and supramolecular polymorphism of aggregated mutant huntingtin exon 1","volume":"432","author":"Boatz","year":"2020","journal-title":"Journal of Molecular Biology"},{"key":"bib11","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01021","article-title":"A meta-analysis of \u03b1-synuclein multiplication in familial parkinsonism","volume":"9","author":"Book","year":"2018","journal-title":"Frontiers in Neurology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.sbi.2020.09.004","article-title":"How do intrinsically disordered protein regions encode a driving force for liquid-liquid phase separation?","volume":"67","author":"Borcherds","year":"2021","journal-title":"Current Opinion in Structural Biology"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1016\/j.cell.2018.10.048","article-title":"Mapping local and global liquid phase behavior in living cells using photo-oligomerizable seeds","volume":"175","author":"Bracha","year":"2018","journal-title":"Cell"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"16392","DOI":"10.1073\/pnas.152330699","article-title":"Interactions among prions and prion \u201cstrains\u201d in yeast","volume":"99 Suppl 4","author":"Bradley","year":"2002","journal-title":"PNAS"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000333","article-title":"BETASCAN: probable beta-amyloids identified by pairwise probabilistic analysis","volume":"5","author":"Bryan","year":"2009","journal-title":"PLOS Computational Biology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"5796","DOI":"10.1073\/pnas.1401587111","article-title":"Structural motif of polyglutamine amyloid fibrils discerned with mixed-isotope infrared spectroscopy","volume":"111","author":"Buchanan","year":"2014","journal-title":"PNAS"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/bs.ircmb.2016.08.014","article-title":"The nucleation of protein aggregates - from crystals to amyloid fibrils","volume":"329","author":"Buell","year":"2017","journal-title":"International Review of Cell and Molecular Biology"},{"key":"bib18","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13210-9","article-title":"Amyloidogenic motifs revealed by n-gram analysis","volume":"7","author":"Burdukiewicz","year":"2017","journal-title":"Scientific Reports"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2020.106520","article-title":"The role of water in the primary nucleation of protein amyloid aggregation","volume":"269","author":"Camino","year":"2021","journal-title":"Biophysical Chemistry"},{"key":"bib20","article-title":"Amber 2020","volume-title":"Amber20","author":"Case","year":"2020","unstructured":"Case DA, Belfon K, Ben-Shalom I, Brozell SR. 2020. Amber 2020. Amber20. https:\/\/ambermd.org\/doc12\/Amber20.pdf."},{"key":"bib21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2207690119","article-title":"Quantitative NMR analysis of the kinetics of prenucleation oligomerization and aggregation of pathogenic huntingtin exon-1 protein","volume":"119","author":"Ceccon","year":"2022","journal-title":"PNAS"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.ygeno.2020.09.065","article-title":"iAMY-SCM: Improved prediction and analysis of amyloid proteins using a scoring card method with propensity scores of dipeptides","volume":"113","author":"Charoenkwan","year":"2021","journal-title":"Genomics"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1006\/jmbi.2001.4850","article-title":"Polyglutamine aggregation behavior in vitro supports a recruitment mechanism of cytotoxicity","volume":"311","author":"Chen","year":"2001","journal-title":"Journal of Molecular Biology"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"11884","DOI":"10.1073\/pnas.182276099","article-title":"Huntington\u2019s disease age-of-onset linked to polyglutamine aggregation nucleation","volume":"99","author":"Chen","year":"2002","journal-title":"PNAS"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1146\/annurev-biochem-061516-045115","article-title":"Protein misfolding, amyloid formation, and human disease: A summary of progress over the last decade","volume":"86","author":"Chiti","year":"2017","journal-title":"Annual Review of Biochemistry"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/0022-2836(77)90094-8","article-title":"Beta-turns in proteins","volume":"115","author":"Chou","year":"1977","journal-title":"Journal of Molecular Biology"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/35018098","article-title":"A one-hit model of cell death in inherited neuronal degenerations","volume":"406","author":"Clarke","year":"2000","journal-title":"Nature"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/nchembio792","article-title":"Stochastic kinetics of intracellular huntingtin aggregate formation","volume":"2","author":"Colby","year":"2006","journal-title":"Nature Chemical Biology"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1126\/science.1138718","article-title":"A general model of prion strains and their pathogenicity","volume":"318","author":"Collinge","year":"2007","journal-title":"Science"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-65","article-title":"AGGRESCAN: a server for the prediction and evaluation of \u201chot spots\u201d of aggregation in polypeptides","volume":"8","author":"Conchillo-Sol\u00e9","year":"2007","journal-title":"BMC Bioinformatics"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"16764","DOI":"10.1073\/pnas.0608175103","article-title":"Fluorescence correlation spectroscopy shows that monomeric polyglutamine molecules form collapsed structures in aqueous solutions","volume":"103","author":"Crick","year":"2006","journal-title":"PNAS"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"20075","DOI":"10.1073\/pnas.1320626110","article-title":"Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation","volume":"110","author":"Crick","year":"2013","journal-title":"PNAS"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.progpolymsci.2015.11.006","article-title":"Polymer spherulites: A critical review","volume":"56","author":"Crist","year":"2016","journal-title":"Progress in Polymer Science"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"e2101","DOI":"10.1212\/WNL.0000000000007147","article-title":"Clinical manifestations of homozygote allele carriers in Huntington disease","volume":"92","author":"Cubo","year":"2019","journal-title":"Neurology"},{"key":"bib35","doi-asserted-by":"publisher","DOI":"10.1101\/2022.08.23.504914","article-title":"In Vivo Suppression of Polyglutamine Aggregation via Co-Condensation of the Molecular Chaperone DNAJB6","volume-title":"bioRxiv","author":"de Mattos","year":"2022"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/s0092-8674(01)00427-5","article-title":"Prions affect the appearance of other prions: the story of [PIN(+)]","volume":"106","author":"Derkatch","year":"2001","journal-title":"Cell"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"28403","DOI":"10.1039\/d2cp02760g","article-title":"Dynamic odd-even effect in n-alkane systems: a molecular dynamics study","volume":"24","author":"Dhiman","year":"2022","journal-title":"Physical Chemistry Chemical Physics"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1146\/annurev-physchem-071819-113553","article-title":"Biomolecular phase separation: From molecular driving forces to macroscopic properties","volume":"71","author":"Dignon","year":"2020","journal-title":"Annual Review of Physical Chemistry"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"12605","DOI":"10.1073\/pnas.0900678106","article-title":"Single homopolypeptide chains collapse into mechanically rigid conformations","volume":"106","author":"Dougan","year":"2009","journal-title":"PNAS"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"11051","DOI":"10.1073\/pnas.0604548103","article-title":"A network of protein interactions determines polyglutamine toxicity","volume":"103","author":"Duennwald","year":"2006","journal-title":"PNAS"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"11045","DOI":"10.1073\/pnas.0604547103","article-title":"Flanking sequences profoundly alter polyglutamine toxicity in yeast","volume":"103","author":"Duennwald","year":"2006","journal-title":"PNAS"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1016\/j.cell.2012.02.022","article-title":"The amyloid state of proteins in human diseases","volume":"148","author":"Eisenberg","year":"2012","journal-title":"Cell"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1146\/annurev-biochem-061516-045104","article-title":"Structural studies of amyloid proteins at the molecular level","volume":"86","author":"Eisenberg","year":"2017","journal-title":"Annual Review of Biochemistry"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41594-023-00920-0","article-title":"The structure of pathogenic huntingtin exon 1 defines the bases of its aggregation propensity","volume":"30","author":"Elena-Real","year":"2023","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.str.2023.04.003","article-title":"Multi-site-specific isotopic labeling accelerates high-resolution structural investigations of pathogenic huntingtin exon-1","volume":"31","author":"Elena-Real","year":"2023","journal-title":"Structure"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0079722","article-title":"MetAmyl: a METa-predictor for AMYLoid proteins","volume":"8","author":"Emily","year":"2013","journal-title":"PLOS ONE"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1021\/ar800217x","article-title":"Nucleation of crystals from solution: classical and two-step models","volume":"42","author":"Erdemir","year":"2009","journal-title":"Accounts of Chemical Research"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"4031","DOI":"10.1529\/biophysj.107.118935","article-title":"Insights into structure, stability, and toxicity of monomeric and aggregated polyglutamine models from molecular dynamics simulations","volume":"94","author":"Esposito","year":"2008","journal-title":"Biophysical Journal"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"The Journal of Chemical Physics"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1038\/nbt1012","article-title":"Prediction of sequence-dependent and mutational effects on the aggregation of peptides and proteins","volume":"22","author":"Fernandez-Escamilla","year":"2004","journal-title":"Nature Biotechnology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1046\/j.1365-2958.2001.02478.x","article-title":"The elimination of the yeast [PSI+] prion by guanidine hydrochloride is the result of Hsp104 inactivation","volume":"40","author":"Ferreira","year":"2001","journal-title":"Molecular Microbiology"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1002\/pro.4105","article-title":"An apparent core\/shell architecture of polyQ aggregates in the aging Caenorhabditis elegans neuron","volume":"30","author":"Fisher","year":"2021","journal-title":"Protein Science"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1021\/sb300028q","article-title":"A basis set of de novo coiled-coil peptide oligomers for rational protein design and synthetic biology","volume":"1","author":"Fletcher","year":"2012","journal-title":"ACS Synthetic Biology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1021\/ja00874a004","article-title":"On the morphology of the crystalline state in polymers","volume":"84","author":"Flory","year":"1962","journal-title":"Journal of the American Chemical Society"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6807-12-18","article-title":"Dependence of \u03b1-helical and \u03b2-sheet amino acid propensities on the overall protein fold type","volume":"12","author":"Fujiwara","year":"2012","journal-title":"BMC Structural Biology"},{"key":"bib56","doi-asserted-by":"publisher","DOI":"10.1002\/pro.4292","article-title":"In vivo liquid-liquid phase separation protects amyloidogenic and aggregation-prone peptides during overexpression in Escherichia coli","volume":"31","author":"Gabryelczyk","year":"2022","journal-title":"Protein Science"},{"key":"bib57","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02360-2","article-title":"Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates","volume":"4","author":"Galaz-Montoya","year":"2021","journal-title":"Communications Biology"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41594-017-0018-0","article-title":"Sub-\u00e5ngstr\u00f6m cryo-EM structure of a prion protofibril reveals a polar clasp","volume":"25","author":"Gallagher-Jones","year":"2018","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib59","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1093\/bioinformatics\/btp691","article-title":"FoldAmyloid: a method of prediction of amyloidogenic regions from protein sequence","volume":"26","author":"Garbuzynskiy","year":"2010","journal-title":"Bioinformatics"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"3487","DOI":"10.1073\/pnas.0915166107","article-title":"Identifying the amylome, proteins capable of forming amyloid-like fibrils","volume":"107","author":"Goldschmidt","year":"2010","journal-title":"PNAS"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1002\/(SICI)1097-0061(199910)15:14<1541::AID-YEA476>3.0.CO;2-K","article-title":"Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae","volume":"15","author":"Goldstein","year":"1999","journal-title":"Yeast"},{"key":"bib62","doi-asserted-by":"publisher","DOI":"10.3791\/838","article-title":"Screening for amyloid aggregation by semi-denaturing detergent-agarose gel electrophoresis","author":"Halfmann","year":"2008","journal-title":"Journal of Visualized Experiments"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.molcel.2011.05.013","article-title":"Opposing effects of glutamine and asparagine govern prion formation by intrinsically disordered proteins","volume":"43","author":"Halfmann","year":"2011","journal-title":"Molecular Cell"},{"key":"bib64","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.ijbiomac.2007.03.008","article-title":"Consensus prediction of amyloidogenic determinants in amyloid fibril-forming proteins","volume":"41","author":"Hamodrakas","year":"2007","journal-title":"International Journal of Biological Macromolecules"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/j.jmb.2006.02.039","article-title":"Standard conformations of beta-arches in beta-solenoid proteins","volume":"358","author":"Hennetin","year":"2006","journal-title":"Journal of Molecular Biology"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1126\/science.aba3526","article-title":"Cryo-EM structure of a neuronal functional amyloid implicated in memory persistence in Drosophila","volume":"367","author":"Hervas","year":"2020","journal-title":"Science"},{"key":"bib67","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43926-9","article-title":"Structural and dynamic studies reveal that the Ala-rich region of ataxin-7 initiates \u03b1-helix formation of the polyQ tract but suppresses its aggregation","volume":"9","author":"Hong","year":"2019","journal-title":"Scientific Reports"},{"key":"bib68","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1073\/pnas.1521933113","article-title":"Huntingtin exon 1 fibrils feature an interdigitated \u03b2-hairpin-based polyglutamine core","volume":"113","author":"Hoop","year":"2016","journal-title":"PNAS"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"17007","DOI":"10.1021\/jacs.7b09362","article-title":"Multistep conformation selection in amyloid assembly","volume":"139","author":"Hsieh","year":"2017","journal-title":"Journal of the American Chemical Society"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"8178","DOI":"10.1021\/ma0344285","article-title":"Intramolecular nucleation model for polymer crystallization","volume":"36","author":"Hu","year":"2003","journal-title":"Macromolecules"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.physrep.2018.04.004","article-title":"The physics of polymer chain-folding","volume":"747","author":"Hu","year":"2018","journal-title":"Physics Reports"},{"key":"bib72","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43059","article-title":"Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in Caenorhabditis elegans","volume":"8","author":"Huang","year":"2019","journal-title":"eLife"},{"key":"bib73","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1021\/acs.jpcb.5b09324","article-title":"How chain-folding crystal growth determines the thermodynamic stability of polymer crystals","volume":"120","author":"Jiang","year":"2016","journal-title":"The Journal of Physical Chemistry. B"},{"key":"bib74","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1111\/tra.12453","article-title":"Polyglutamine toxicity in yeast uncovers phenotypic variations between different fluorescent protein fusions","volume":"18","author":"Jiang","year":"2017","journal-title":"Traffic"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.molcel.2016.03.017","article-title":"The S\/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the Onset of Disease in a Mouse Model","volume":"62","author":"Kakkar","year":"2016","journal-title":"Molecular Cell"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"8820","DOI":"10.1021\/jacs.7b00838","article-title":"Emerging \u03b2-Sheet Rich Conformations in Supercompact Huntingtin Exon-1 Mutant Structures","volume":"139","author":"Kang","year":"2017","journal-title":"Journal of the American Chemical Society"},{"key":"bib77","doi-asserted-by":"publisher","DOI":"10.1063\/1.5029369","article-title":"Glassy dynamics in mutant huntingtin proteins","volume":"149","author":"Kang","year":"2018","journal-title":"The Journal of Chemical Physics"},{"key":"bib78","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/nsmb.1992","article-title":"Critical nucleus size for disease-related polyglutamine aggregation is repeat-length dependent","volume":"18","author":"Kar","year":"2011","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib79","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05829-5","article-title":"Heterologous prion-forming proteins interact to cross-seed aggregation in Saccharomyces cerevisiae","volume":"7","author":"Keefer","year":"2017","journal-title":"Scientific Reports"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1038\/1801289a0","article-title":"Large periods in polyethylene: The origin of low-angle x-ray scattering","volume":"180","author":"Keller","year":"1957","journal-title":"Nature"},{"key":"bib81","doi-asserted-by":"publisher","DOI":"10.3390\/biom11040500","article-title":"The budapest amyloid predictor and its applications","volume":"11","author":"Keresztes","year":"2021","journal-title":"Biomolecules"},{"key":"bib82","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1143353","article-title":"Comparative molecular dynamics simulations of pathogenic and non-pathogenic huntingtin protein monomers and dimers","volume":"10","author":"Khaled","year":"2023","journal-title":"Frontiers in Molecular Biosciences"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.molcel.2018.06.016","article-title":"Quantifying nucleation in vivo reveals the physical basis of prion-like phase behavior","volume":"71","author":"Khan","year":"2018","journal-title":"Molecular Cell"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"W469","DOI":"10.1093\/nar\/gkp351","article-title":"NetCSSP: web application for predicting chameleon sequences and amyloid fibril formation","volume":"37","author":"Kim","year":"2009","journal-title":"Nucleic Acids Research"},{"key":"bib85","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.molcel.2016.07.022","article-title":"Soluble Oligomers of PolyQ-Expanded Huntingtin Target a Multiplicity of Key Cellular Factors","volume":"63","author":"Kim","year":"2016","journal-title":"Molecular Cell"},{"key":"bib86","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.neuron.2020.08.022","article-title":"Als genetics: Gains, losses, and implications for future therapies","volume":"108","author":"Kim","year":"2020","journal-title":"Neuron"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1126\/science.aav6691","article-title":"Phase separation provides a mechanism to reduce noise in cells","volume":"367","author":"Klosin","year":"2020","journal-title":"Science"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1126\/science.1178250","article-title":"An analytical solution to the kinetics of breakable filament assembly","volume":"326","author":"Knowles","year":"2009","journal-title":"Science"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"49636","DOI":"10.1074\/jbc.M307996200","article-title":"Yeast [PSI+] prion aggregates are formed by small Sup35 polymers fragmented by Hsp104","volume":"278","author":"Kryndushkin","year":"2003","journal-title":"The Journal of Biological Chemistry"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"27100","DOI":"10.1074\/jbc.M113.485359","article-title":"Non-targeted identification of prions and amyloid-forming proteins from yeast and mammalian cells","volume":"288","author":"Kryndushkin","year":"2013","journal-title":"The Journal of Biological Chemistry"},{"key":"bib91","doi-asserted-by":"publisher","first-page":"4373","DOI":"10.1039\/d0sc04395h","article-title":"Sequestration within biomolecular condensates inhibits A\u03b2-42 amyloid formation","volume":"12","author":"K\u00fcffner","year":"2021","journal-title":"Chemical Science"},{"key":"bib92","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2017.00145","article-title":"Chaperones in Polyglutamine Aggregation: Beyond the Q-Stretch","volume":"11","author":"Kuiper","year":"2017","journal-title":"Frontiers in Neuroscience"},{"key":"bib93","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s00439-011-1101-y","article-title":"Epigenetics DNA methylation in the core ataxin-2 gene promoter: novel physiological and pathological implications","volume":"131","author":"Laffita-Mesa","year":"2012","journal-title":"Human Genetics"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1038\/nmeth.1955","article-title":"Segregation of molecules at cell division reveals native protein localization","volume":"9","author":"Landgraf","year":"2012","journal-title":"Nature Methods"},{"key":"bib95","doi-asserted-by":"publisher","first-page":"73","DOI":"10.6028\/jres.064A.007","article-title":"Theory of formation of polymer crystals with folded chains in dilute solution","volume":"64A","author":"Lauritzen","year":"1960","journal-title":"Journal of Research of the National Bureau of Standards. Section A, Physics and Chemistry"},{"key":"bib96","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.cell.2019.06.036","article-title":"CAG repeat not polyglutamine length determines timing of huntington\u2019s disease onset","volume":"178","author":"Lee","year":"2019","journal-title":"Cell"},{"key":"bib97","doi-asserted-by":"publisher","first-page":"14777","DOI":"10.1074\/jbc.M109.093708","article-title":"Mutant huntingtin fragments form oligomers in a polyglutamine length-dependent manner in vitro and in vivo","volume":"285","author":"Legleiter","year":"2010","journal-title":"Journal of Biological Chemistry"},{"key":"bib98","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3753","article-title":"Soluble forms of polyQ-expanded huntingtin rather than large aggregates cause endoplasmic reticulum stress","volume":"4","author":"Leitman","year":"2013","journal-title":"Nature Communications"},{"key":"bib99","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms6219","article-title":"Ostwald\u2019s rule of stages governs structural transitions and morphology of dipeptide supramolecular polymers","volume":"5","author":"Levin","year":"2014","journal-title":"Nature Communications"},{"key":"bib100","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/1097-0290(20001020)70:2<187::aid-bit8>3.0.co;2-h","article-title":"Green fluorescent protein in Saccharomyces cerevisiae: real-time studies of the GAL1 promoter","volume":"70","author":"Li","year":"2000","journal-title":"Biotechnology and Bioengineering"},{"key":"bib101","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1126\/science.1183218","article-title":"Darwinian evolution of prions in cell culture","volume":"327","author":"Li","year":"2010","journal-title":"Science"},{"key":"bib102","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.sbi.2018.04.004","article-title":"Conformational evolution of polymorphic amyloid assemblies","volume":"51","author":"Liang","year":"2018","journal-title":"Current Opinion in Structural Biology"},{"key":"bib103","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev-pathmechdis-012418-012857","article-title":"Polyglutamine repeats in neurodegenerative diseases","volume":"14","author":"Lieberman","year":"2019","journal-title":"Annual Review of Pathology"},{"key":"bib104","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15462","article-title":"Fibril polymorphism affects immobilized non-amyloid flanking domains of huntingtin exon1 rather than its polyglutamine core","volume":"8","author":"Lin","year":"2017","journal-title":"Nature Communications"},{"key":"bib105","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-019-0411-9","article-title":"Automated four-dimensional long term imaging enables single cell tracking within organotypic brain slices to study neurodevelopment and degeneration","volume":"2","author":"Linsley","year":"2019","journal-title":"Communications Biology"},{"key":"bib106","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abq6495","article-title":"Biomolecular condensates can both accelerate and suppress aggregation of \u03b1-synuclein","volume":"8","author":"Lipi\u0144ski","year":"2022","journal-title":"Science Advances"},{"key":"bib107","doi-asserted-by":"publisher","first-page":"1820","DOI":"10.1096\/fj.12-219220","article-title":"A novel human embryonic stem cell-derived Huntington\u2019s disease neuronal model exhibits mutant huntingtin (mHTT) aggregates and soluble mHTT-dependent neurodegeneration","volume":"27","author":"Lu","year":"2013","journal-title":"FASEB Journal"},{"key":"bib108","doi-asserted-by":"publisher","first-page":"3696","DOI":"10.1021\/acs.jctc.5b00255","article-title":"ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB","volume":"11","author":"Maier","year":"2015","journal-title":"Journal of Chemical Theory and Computation"},{"key":"bib109","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1021\/cn500358g","article-title":"Structural determinants of polyglutamine protofibrils and crystallites","volume":"6","author":"Man","year":"2015","journal-title":"ACS Chemical Neuroscience"},{"key":"bib110","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1017\/S0033583508004733","article-title":"Fibrils with parallel in-register structure constitute a major class of amyloid fibrils: molecular insights from electron paramagnetic resonance spectroscopy","volume":"41","author":"Margittai","year":"2008","journal-title":"Quarterly Reviews of Biophysics"},{"key":"bib111","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24411-2","article-title":"Huntingtin fibrils with different toxicity, structure, and seeding potential can be interconverted","volume":"12","author":"Mario Isas","year":"2021","journal-title":"Nature Communications"},{"key":"bib112","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1212\/wnl.57.8.1502","article-title":"Pathogenic effect of an intermediate-size SCA-6 allele (CAG)(19) in a homozygous patient","volume":"57","author":"Mariotti","year":"2001","journal-title":"Neurology"},{"key":"bib113","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1177\/1535370219856620","article-title":"Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington\u2019s disease","volume":"244","author":"Matlahov","year":"2019","journal-title":"Experimental Biology and Medicine"},{"key":"bib114","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nmeth.1432","article-title":"Exploring the sequence determinants of amyloid structure using position-specific scoring matrices","volume":"7","author":"Maurer-Stroh","year":"2010","journal-title":"Nature Methods"},{"key":"bib115","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003648","article-title":"The role of interruptions in polyQ in the pathology of SCA1","volume":"9","author":"Menon","year":"2013","journal-title":"PLOS Genetics"},{"key":"bib116","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1083\/jcb.200112104","article-title":"Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1","volume":"157","author":"Meriin","year":"2002","journal-title":"The Journal of Cell Biology"},{"key":"bib117","doi-asserted-by":"publisher","DOI":"10.1088\/1361-648X\/aa5f10","article-title":"Physical principles of filamentous protein self-assembly kinetics","volume":"29","author":"Michaels","year":"2017","journal-title":"Journal of Physics. Condensed Matter"},{"key":"bib118","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1038\/s42254-023-00598-9","article-title":"Amyloid formation as a protein phase transition","volume":"5","author":"Michaels","year":"2023","journal-title":"Nature Reviews Physics"},{"key":"bib119","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.csbj.2020.01.012","article-title":"The importance of definitions in the study of polyQ regions: A tale of thresholds, impurities and sequence context","volume":"18","author":"Mier","year":"2020","journal-title":"Computational and Structural Biotechnology Journal"},{"key":"bib120","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1038\/nchembio.694","article-title":"Identifying polyglutamine protein species in situ that best predict neurodegeneration","volume":"7","author":"Miller","year":"2011","journal-title":"Nature Chemical Biology"},{"key":"bib121","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1002501","article-title":"Are long-range structural correlations behind the aggregration phenomena of polyglutamine diseases?","volume":"8","author":"Moradi","year":"2012","journal-title":"PLOS Computational Biology"},{"key":"bib122","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/s10930-020-09880-6","article-title":"Propensities of amino acid pairings in secondary structure of globular proteins","volume":"39","author":"Nacar","year":"2020","journal-title":"The Protein Journal"},{"key":"bib123","doi-asserted-by":"publisher","first-page":"10723","DOI":"10.1021\/jacs.2c00509","article-title":"Structural Basis of Huntingtin Fibril Polymorphism Revealed by Cryogenic Electron Microscopy of Exon 1 HTT Fibrils","volume":"144","author":"Nazarov","year":"2022","journal-title":"Journal of the American Chemical Society"},{"key":"bib124","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00200","article-title":"PolyQ Tract Toxicity in SCA1 is Length Dependent in the Absence of CAG Repeat Interruption","volume":"12","author":"Nethisinghe","year":"2018","journal-title":"Frontiers in Cellular Neuroscience"},{"key":"bib125","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1016\/j.jmb.2018.03.031","article-title":"Tadpole-like conformations of huntingtin exon 1 are characterized by conformational heterogeneity that persists regardless of polyglutamine length","volume":"430","author":"Newcombe","year":"2018","journal-title":"Journal of Molecular Biology"},{"key":"bib126","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116003","article-title":"Proteomic screening for amyloid proteins","volume":"9","author":"Nizhnikov","year":"2014","journal-title":"PLOS ONE"},{"key":"bib127","doi-asserted-by":"publisher","first-page":"i34","DOI":"10.1093\/bioinformatics\/btr238","article-title":"A method for probing the mutational landscape of amyloid structure","volume":"27","author":"O\u2019Donnell","year":"2011","journal-title":"Bioinformatics"},{"key":"bib128","doi-asserted-by":"publisher","first-page":"21807","DOI":"10.1074\/jbc.M109.084434","article-title":"Tracking mutant huntingtin aggregation kinetics in cells reveals three major populations that include an invariant oligomer pool","volume":"285","author":"Olshina","year":"2010","journal-title":"The Journal of Biological Chemistry"},{"key":"bib129","doi-asserted-by":"publisher","first-page":"1995","DOI":"10.1021\/ma00194a078","article-title":"Rate minimum in solution crystallization of long paraffins","volume":"22","author":"Organ","year":"1989","journal-title":"Macromolecules"},{"key":"bib130","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0020086","article-title":"Dissection and design of yeast prions","volume":"2","author":"Osherovich","year":"2004","journal-title":"PLOS Biology"},{"key":"bib131","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a033860","article-title":"Functional amyloids","volume":"11","author":"Otzen","year":"2019","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"bib132","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1021\/acs.macromol.0c02374","article-title":"Even\u2013Odd Effect in Aliphatic Polycarbonates with Different Chain Lengths: from Poly (Hexamethylene Carbonate) to Poly (Dodecamethylene Carbonate)","volume":"54","author":"P\u00e9rez-Camargo","year":"2021","journal-title":"Macromolecules"},{"key":"bib133","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.molcel.2018.04.007","article-title":"A liquid to solid phase transition underlying pathological huntingtin exon1 aggregation","volume":"70","author":"Peskett","year":"2018","journal-title":"Molecular Cell"},{"key":"bib134","doi-asserted-by":"publisher","first-page":"2989","DOI":"10.1016\/j.bpj.2020.05.013","article-title":"Thermodynamics of huntingtin aggregation","volume":"118","author":"Phan","year":"2020","journal-title":"Biophysical Journal"},{"key":"bib135","doi-asserted-by":"publisher","first-page":"2931","DOI":"10.1016\/j.bpj.2022.06.031","article-title":"Conformational entropy limits the transition from nucleation to elongation in amyloid aggregation","volume":"121","author":"Phan","year":"2022","journal-title":"Biophysical Journal"},{"key":"bib136","doi-asserted-by":"publisher","first-page":"3734","DOI":"10.1074\/jbc.RA117.000357","article-title":"Profilin reduces aggregation and phase separation of huntingtin N-terminal fragments by preferentially binding to soluble monomers and oligomers","volume":"293","author":"Posey","year":"2018","journal-title":"The Journal of Biological Chemistry"},{"key":"bib137","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.166848","article-title":"Mechanistic inferences from analysis of measurements of protein phase transitions in live cells","volume":"433","author":"Posey","year":"2021","journal-title":"Journal of Molecular Biology"},{"key":"bib138","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s12551-021-00778-w","article-title":"Protein aggregation: in silico algorithms and applications","volume":"13","author":"Prabakaran","year":"2021","journal-title":"Biophysical Reviews"},{"key":"bib139","doi-asserted-by":"publisher","first-page":"10096","DOI":"10.1063\/1.1808117","article-title":"A modified TIP3P water potential for simulation with Ewald summation","volume":"121","author":"Price","year":"2004","journal-title":"The Journal of Chemical Physics"},{"key":"bib140","doi-asserted-by":"publisher","first-page":"1944","DOI":"10.1021\/acs.jpclett.8b00348","article-title":"Interaction enthalpy of side chain and backbone amides in polyglutamine solution monomers and fibrils","volume":"9","author":"Punihaole","year":"2018","journal-title":"The Journal of Physical Chemistry Letters"},{"key":"bib141","doi-asserted-by":"publisher","DOI":"10.1002\/syst.202000050","article-title":"In Cellulo Analysis of Huntingtin Inclusion Bodies by Cryogenic Nanoprobe SAXS","volume":"3","author":"Rumancev","year":"2021","journal-title":"ChemSystemsChem"},{"key":"bib142","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/0032-3861(83)90220-3","article-title":"Roughness of growth faces of polymer crystals: Evidence from morphology and implications for growth mechanisms and types of folding","volume":"24","author":"Sadler","year":"1983","journal-title":"Polymer"},{"key":"bib143","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.neuron.2014.04.047","article-title":"Distinct tau prion strains propagate in cells and mice and define different tauopathies","volume":"82","author":"Sanders","year":"2014","journal-title":"Neuron"},{"key":"bib144","doi-asserted-by":"publisher","DOI":"10.1063\/1.4965040","article-title":"Kinetics of spontaneous filament nucleation via oligomers: Insights from theory and simulation","volume":"145","author":"\u0160ari\u0107","year":"2016","journal-title":"The Journal of Chemical Physics"},{"key":"bib145","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1093\/hmg\/ddp467","article-title":"Identical oligomeric and fibrillar structures captured from the brains of R6\/2 and knock-in mouse models of Huntington\u2019s disease","volume":"19","author":"Sathasivam","year":"2010","journal-title":"Human Molecular Genetics"},{"key":"bib146","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nature05695","article-title":"Atomic structures of amyloid cross-beta spines reveal varied steric zippers","volume":"447","author":"Sawaya","year":"2007","journal-title":"Nature"},{"key":"bib147","doi-asserted-by":"publisher","first-page":"4857","DOI":"10.1016\/j.cell.2021.08.013","article-title":"The expanding amyloid family: Structure, stability, function, and pathogenesis","volume":"184","author":"Sawaya","year":"2021","journal-title":"Cell"},{"key":"bib148","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jmb.2011.06.045","article-title":"Structural Characterization of Polyglutamine Fibrils by Solid-State NMR Spectroscopy","volume":"412","author":"Schneider","year":"2011","journal-title":"Journal of Molecular Biology"},{"key":"bib149","doi-asserted-by":"publisher","first-page":"595","DOI":"10.15252\/emmm.201606210","article-title":"The amyloid hypothesis of Alzheimer\u2019s disease at 25 years","volume":"8","author":"Selkoe","year":"2016","journal-title":"EMBO Molecular Medicine"},{"key":"bib150","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1110\/ps.0224403","article-title":"Role of histidine interruption in mitigating the pathological effects of long polyglutamine stretches in SCA1: A molecular approach","volume":"12","author":"Sen","year":"2003","journal-title":"Protein Science"},{"key":"bib151","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1126\/science.289.5483.1317","article-title":"Nucleated conformational conversion and the replication of conformational information by a prion determinant","volume":"289","author":"Serio","year":"2000","journal-title":"Science"},{"key":"bib152","doi-asserted-by":"publisher","DOI":"10.1093\/femsyr\/foy026","article-title":"[PIN+]ing down the mechanism of prion appearance","volume":"18","author":"Serio","year":"2018","journal-title":"FEMS Yeast Research"},{"key":"bib153","doi-asserted-by":"publisher","DOI":"10.1038\/srep18407","article-title":"A protein polymerization cascade mediates toxicity of non-pathological human huntingtin in yeast","volume":"5","author":"Serpionov","year":"2015","journal-title":"Scientific Reports"},{"key":"bib154","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1002\/prot.20602","article-title":"Polyglutamine homopolymers having 8-45 residues form slablike beta-crystallite assemblies","volume":"61","author":"Sharma","year":"2005","journal-title":"Proteins"},{"key":"bib155","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1021\/bm0494388","article-title":"New model for crystalline polyglutamine assemblies and their connection with amyloid fibrils","volume":"6","author":"Sikorski","year":"2005","journal-title":"Biomacromolecules"},{"key":"bib156","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.bpj.2017.12.023","article-title":"Quantitative characterization of metastability and heterogeneity of amyloid aggregates","volume":"114","author":"Sil","year":"2018","journal-title":"Biophysical Journal"},{"key":"bib157","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.jsb.2017.09.006","article-title":"Polyglutamine expansion diseases: More than simple repeats","volume":"201","author":"Silva","year":"2018","journal-title":"Journal of Structural Biology"},{"key":"bib158","doi-asserted-by":"publisher","DOI":"10.1186\/s40659-016-0092-5","article-title":"50 years of amino acid hydrophobicity scales: revisiting the capacity for peptide classification","volume":"49","author":"Simm","year":"2016","journal-title":"Biological Research"},{"key":"bib159","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2021888118","article-title":"Kinetic analysis reveals that independent nucleation events determine the progression of polyglutamine aggregation in C. elegans","volume":"118","author":"Sinnige","year":"2021","journal-title":"PNAS"},{"key":"bib160","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1083\/jcb.200306020","article-title":"Formation of stacked ER cisternae by low affinity protein interactions","volume":"163","author":"Snapp","year":"2003","journal-title":"The Journal of Cell Biology"},{"key":"bib161","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.jns.2016.12.051","article-title":"Gene dosage effect in spinocerebellar ataxia type 6 homozygotes: A clinical and neuropathological study","volume":"373","author":"Soga","year":"2017","journal-title":"Journal of the Neurological Sciences"},{"key":"bib162","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1111\/j.1399-0004.2007.00868.x","article-title":"Gene dosage influences the age at onset of SCA2 in a family from southern Italy","volume":"72","author":"Spadafora","year":"2007","journal-title":"Clinical Genetics"},{"key":"bib163","doi-asserted-by":"publisher","DOI":"10.1080\/21690707.2015.1056905","article-title":"Collapsed state of polyglutamic acid results in amyloid spherulite formation","volume":"3","author":"Stehli","year":"2015","journal-title":"Intrinsically Disordered Proteins"},{"key":"bib164","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.sbi.2020.10.019","article-title":"Amyloid aggregation simulations: challenges, advances and perspectives","volume":"67","author":"Strodel","year":"2021","journal-title":"Current Opinion in Structural Biology"},{"key":"bib165","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1093\/hmg\/ddm311","article-title":"Soluble polyglutamine oligomers formed prior to inclusion body formation are cytotoxic","volume":"17","author":"Takahashi","year":"2008","journal-title":"Human Molecular Genetics"},{"key":"bib166","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/nature04922","article-title":"The physical basis of how prion conformations determine strain phenotypes","volume":"442","author":"Tanaka","year":"2006","journal-title":"Nature"},{"key":"bib167","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1021\/cr050258d","article-title":"Understanding odd-even effects in organic self-assembled monolayers","volume":"107","author":"Tao","year":"2007","journal-title":"Chemical Reviews"},{"key":"bib168","doi-asserted-by":"publisher","first-page":"17014","DOI":"10.1073\/pnas.252523899","article-title":"Mutational analysis of the structural organization of polyglutamine aggregates","volume":"99","author":"Thakur","year":"2002","journal-title":"PNAS"},{"key":"bib169","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.1093\/bioinformatics\/btu167","article-title":"GAP: towards almost 100 percent prediction for \u03b2-strand-mediated aggregating peptides with distinct morphologies","volume":"30","author":"Thangakani","year":"2014","journal-title":"Bioinformatics"},{"key":"bib170","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000283","article-title":"Homozygous 31 trinucleotide repeats in the SCA2 allele are pathogenic for cerebellar ataxia","volume":"4","author":"Tojima","year":"2018","journal-title":"Neurology. Genetics"},{"key":"bib171","doi-asserted-by":"publisher","first-page":"8667","DOI":"10.1039\/C8CC02204F","article-title":"Secondary nucleation in amyloid formation","volume":"54","author":"T\u00f6rnquist","year":"2018","journal-title":"Chemical Communications"},{"key":"bib172","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1016\/0032-3861(87)90298-9","article-title":"Inversion of the temperature dependence of crystallization rates due to onset of chain folding","volume":"28","author":"Ungar","year":"1987","journal-title":"Polymer"},{"key":"bib173","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/b107232","volume-title":"Interphases and Mesophases in Polymer Crystallization I, Advances in Polymer Science","author":"Ungar","year":"2005"},{"key":"bib174","doi-asserted-by":"publisher","DOI":"10.1088\/0953-8984\/24\/19\/193101","article-title":"Phase diagrams and kinetics of phase transitions in protein solutions","volume":"24","author":"Vekilov","year":"2012","journal-title":"Journal of Physics. Condensed Matter"},{"key":"bib175","doi-asserted-by":"publisher","DOI":"10.3791\/59577","article-title":"Detecting and characterizing protein self-assembly in vivo by flow cytometry","author":"Venkatesan","year":"2019","journal-title":"Journal of Visualized Experiments"},{"key":"bib176","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/nsmb.2030","article-title":"Strain conformation, primary structure and the propagation of the yeast prion [PSI+]","volume":"18","author":"Verges","year":"2011","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib177","doi-asserted-by":"publisher","first-page":"2448","DOI":"10.1016\/j.febslet.2015.07.006","article-title":"The route to protein aggregate superstructures: Particulates and amyloid\u2010like spherulites","volume":"589","author":"Vetri","year":"2015","journal-title":"FEBS Letters"},{"key":"bib178","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1529\/biophysj.107.110080","article-title":"Quantitative characterization of intrinsic disorder in polyglutamine: insights from analysis based on polymer theories","volume":"93","author":"Vitalis","year":"2007","journal-title":"Biophysical Journal"},{"key":"bib179","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.bpc.2011.04.006","article-title":"Assessing the contribution of heterogeneous distributions of oligomers to aggregation mechanisms of polyglutamine peptides","volume":"159","author":"Vitalis","year":"2011","journal-title":"Biophysical Chemistry"},{"key":"bib180","doi-asserted-by":"publisher","first-page":"W301","DOI":"10.1093\/nar\/gku399","article-title":"PASTA 2.0: an improved server for protein aggregation prediction","volume":"42","author":"Walsh","year":"2014","journal-title":"Nucleic Acids Research"},{"key":"bib181","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/j.jmb.2009.08.034","article-title":"Examining polyglutamine peptide length: A connection between collapsed conformations and increased aggregation","volume":"393","author":"Walters","year":"2009","journal-title":"Journal of Molecular Biology"},{"key":"bib182","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.jmb.2012.03.017","article-title":"Elongation kinetics of polyglutamine peptide fibrils: a quartz crystal microbalance with dissipation study","volume":"421","author":"Walters","year":"2012","journal-title":"Journal of Molecular Biology"},{"key":"bib183","doi-asserted-by":"publisher","DOI":"10.1101\/2021.02.25.432866","article-title":"A Precise and General FRET-Based Method for Monitoring Structural Transitions in Protein Self-Organization","volume-title":"bioRxiv","author":"Wan","year":"2021"},{"key":"bib184","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1002\/prot.20761","article-title":"Characterizing the conformational ensemble of monomeric polyglutamine","volume":"63","author":"Wang","year":"2006","journal-title":"Proteins"},{"key":"bib185","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1038\/nchem.2803","article-title":"Phase behaviour of disordered proteins underlying low density and high permeability of liquid organelles","volume":"9","author":"Wei","year":"2017","journal-title":"Nature Chemistry"},{"key":"bib186","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/nchembio0606-297","article-title":"Nucleation of huntingtin aggregation in cells","volume":"2","author":"Wetzel","year":"2006","journal-title":"Nature Chemical Biology"},{"key":"bib187","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1021\/acs.accounts.0c00450","article-title":"Exploding the repeat length paradigm while exploring amyloid toxicity in huntington\u2019s disease","volume":"53","author":"Wetzel","year":"2020","journal-title":"Accounts of Chemical Research"},{"key":"bib188","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/326194a0","article-title":"Homozygotes for Huntington\u2019s disease","volume":"326","author":"Wexler","year":"1987","journal-title":"Nature"},{"key":"bib189","doi-asserted-by":"publisher","DOI":"10.1063\/1.4941457","article-title":"Minimal physical requirements for crystal growth self-poisoning","volume":"144","author":"Whitelam","year":"2016","journal-title":"The Journal of Chemical Physics"},{"key":"bib190","doi-asserted-by":"publisher","DOI":"10.3390\/cryst11030304","article-title":"Concepts of nucleation in polymer crystallization","volume":"11","author":"Xu","year":"2021","journal-title":"Crystals"},{"key":"bib191","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.jmb.2005.07.061","article-title":"Seeding-dependent propagation and maturation of amyloid fibril conformation","volume":"352","author":"Yamaguchi","year":"2005","journal-title":"Journal of Molecular Biology"},{"key":"bib192","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.00754","article-title":"Phase transition of huntingtin: Factors and pathological relevance","volume":"11","author":"Yang","year":"2020","journal-title":"Frontiers in Genetics"},{"key":"bib193","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1016\/j.bpj.2020.03.023","article-title":"Amyloid evolution: Antiparallel replaced by parallel","volume":"118","author":"Zanjani","year":"2020","journal-title":"Biophysical Journal"},{"key":"bib194","doi-asserted-by":"publisher","DOI":"10.3390\/cryst7010004","article-title":"A review on polymer crystallization theories","volume":"7","author":"Zhang","year":"2016","journal-title":"Crystals"},{"key":"bib195","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1021\/acschemneuro.5b00337","article-title":"Amyloid properties of asparagine and glutamine in prion-like proteins","volume":"7","author":"Zhang","year":"2016","journal-title":"ACS Chemical Neuroscience"},{"key":"bib196","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.93.060401","article-title":"Pseudo-one-dimensional nucleation in dilute polymer solutions","volume":"93","author":"Zhang","year":"2016","journal-title":"Physical Review. E"},{"key":"bib197","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1021\/acs.macromol.7b02745","article-title":"Effect of self-poisoning on crystallization kinetics of dimorphic precision polyethylenes with bromine","volume":"51","author":"Zhang","year":"2018","journal-title":"Macromolecules"},{"key":"bib198","doi-asserted-by":"publisher","first-page":"7899","DOI":"10.1021\/acs.macromol.0c01443","article-title":"Crystallization of long-spaced precision polyacetals ii: Effect of polymorphism on isothermal crystallization kinetics","volume":"53","author":"Zhang","year":"2020","journal-title":"Macromolecules"},{"key":"bib199","doi-asserted-by":"publisher","DOI":"10.1002\/pcr2.10173","article-title":"Secondary nucleation in polymer crystallization: A kinetic view","volume":"4","author":"Zhang","year":"2021","journal-title":"Polymer crystallization"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/86939\/elife-86939-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/86939\/elife-86939-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/86939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T10:35:52Z","timestamp":1699007752000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/86939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":199,"alternative-id":["10.7554\/eLife.86939"],"URL":"https:\/\/doi.org\/10.7554\/elife.86939","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.7554\/eLife.86939.2","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2023.03.20.533418","asserted-by":"subject"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.86939.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.86939.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.86939.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"LIBPB-1494","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,3]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP86939"}}