{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:10:20Z","timestamp":1790878220180,"version":"4.1.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T00:00:00Z","timestamp":1689897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001869","name":"Academia Sinica","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001869","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Abnormal polyglutamine (polyQ) expansion and fibrillization occur in Huntington\u2019s disease (HD). Amyloid modifier SERF enhances amyloid formation, but the underlying mechanism is not revealed. Here, the fibrillization and toxicity effect of SERF1a on Htt-exon1 are examined. SERF1a enhances the fibrillization of and interacts with mutant thioredoxin (Trx)-fused Httex1. NMR studies with Htt peptides show that TrxHttex1-39Q interacts with the helical regions in SERF1a and SERF1a preferentially interacts with the N-terminal 17 residues of Htt. Time-course analysis shows that SERF1a induces mutant TrxHttex1 to a single conformation enriched of \u03b2-sheet. Co-expression of SERF1a and Httex1-polyQ in neuroblastoma and lentiviral infection of SERF1a in HD-induced polypotent stem cell (iPSC)-derived neurons demonstrates the detrimental effect of SERF1a in HD. Higher level of SERF1a transcript or protein is detected in HD iPSC, transgenic mice, and HD plasma. Overall, this study provides molecular mechanism for SERF1a and mutant Httex1 to facilitate therapeutic development for HD.<\/jats:p>","DOI":"10.1038\/s42003-023-05142-0","type":"journal-article","created":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T18:02:36Z","timestamp":1689962556000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Amyloid modifier SERF1a interacts with polyQ-expanded huntingtin-exon 1 via helical interactions and exacerbates polyQ-induced toxicity"],"prefix":"10.1038","volume":"6","author":[{"given":"Tien-Ying","family":"Tsai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Wei","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien-Chang","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Lan","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orion","family":"Shih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Chung","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiung-Mei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U-Ser","family":"Jeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Chih","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Fon","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6596-6338","authenticated-orcid":false,"given":"Yun-Ru","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,7,21]]},"reference":[{"key":"5142_CR1","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1038\/s41580-018-0060-8","volume":"19","author":"MG Iadanza","year":"2018","unstructured":"Iadanza, M. G., Jackson, M. P., Hewitt, E. W., Ranson, N. A. & Radford, S. E. A new era for understanding amyloid structures and disease. Nat. Rev. Mol. Cell Biol. 19, 755\u2013773 (2018).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"5142_CR2","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1146\/annurev.neuro.29.051605.113042","volume":"30","author":"HT Orr","year":"2007","unstructured":"Orr, H. T. & Zoghbi, H. Y. Trinucleotide repeat disorders. Annu Rev. Neurosci. 30, 575\u2013621 (2007).","journal-title":"Annu Rev. Neurosci."},{"key":"5142_CR3","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/S0092-8674(00)80514-0","volume":"90","author":"E Scherzinger","year":"1997","unstructured":"Scherzinger, E. et al. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90, 549\u2013558 (1997).","journal-title":"Cell"},{"key":"5142_CR4","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/S0962-8924(00)01853-5","volume":"10","author":"AJ Tobin","year":"2000","unstructured":"Tobin, A. J. & Signer, E. R. Huntington\u2019s disease: the challenge for cell biologists. Trends Cell Biol. 10, 531\u2013536 (2000).","journal-title":"Trends Cell Biol."},{"key":"5142_CR5","doi-asserted-by":"publisher","first-page":"7391","DOI":"10.1021\/bi011772q","volume":"41","author":"S Chen","year":"2002","unstructured":"Chen, S., Berthelier, V., Hamilton, J. B., O\u2019Nuallain, B. & Wetzel, R. Amyloid-like features of polyglutamine aggregates and their assembly kinetics. Biochemistry 41, 7391\u20137399 (2002).","journal-title":"Biochemistry"},{"key":"5142_CR6","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1177\/1535370219856620","volume":"244","author":"I Matlahov","year":"2019","unstructured":"Matlahov, I. & van der Wel, P. C. Conformational studies of pathogenic expanded polyglutamine protein deposits from Huntington\u2019s disease. Exp. Biol. Med (Maywood) 244, 1584\u20131595 (2019).","journal-title":"Exp. Biol. Med (Maywood)"},{"key":"5142_CR7","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/ng0298-150","volume":"18","author":"D Martindale","year":"1998","unstructured":"Martindale, D. et al. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat. Genet 18, 150\u2013154 (1998).","journal-title":"Nat. Genet"},{"key":"5142_CR8","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1038\/nm1113","volume":"10","author":"MS Forman","year":"2004","unstructured":"Forman, M. S., Trojanowski, J. Q. & Lee, V. M. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat. Med 10, 1055\u20131063 (2004).","journal-title":"Nat. Med"},{"key":"5142_CR9","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1093\/hmg\/ddp467","volume":"19","author":"K Sathasivam","year":"2010","unstructured":"Sathasivam, K. et al. Identical oligomeric and fibrillar structures captured from the brains of R6\/2 and knock-in mouse models of Huntington\u2019s disease. Hum. Mol. Genet 19, 65\u201378 (2010).","journal-title":"Hum. Mol. Genet"},{"key":"5142_CR10","doi-asserted-by":"publisher","first-page":"14777","DOI":"10.1074\/jbc.M109.093708","volume":"285","author":"J Legleiter","year":"2010","unstructured":"Legleiter, J. et al. Mutant huntingtin fragments form oligomers in a polyglutamine length-dependent manner in vitro and in vivo. J. Biol. Chem. 285, 14777\u201314790 (2010).","journal-title":"J. Biol. Chem."},{"key":"5142_CR11","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1016\/j.celrep.2017.04.029","volume":"19","author":"YM Ramdzan","year":"2017","unstructured":"Ramdzan, Y. M. et al. Huntingtin Inclusions Trigger Cellular Quiescence, Deactivate Apoptosis, and Lead to Delayed Necrosis. Cell Rep. 19, 919\u2013927 (2017).","journal-title":"Cell Rep."},{"key":"5142_CR12","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1038\/nchembio.694","volume":"7","author":"J Miller","year":"2011","unstructured":"Miller, J. et al. Identifying polyglutamine protein species in situ that best predict neurodegeneration. Nat. Chem. Biol. 7, 925\u2013934 (2011).","journal-title":"Nat. Chem. Biol."},{"key":"5142_CR13","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nsmb1215","volume":"14","author":"Y Nagai","year":"2007","unstructured":"Nagai, Y. et al. A toxic monomeric conformer of the polyglutamine protein. Nat. Struct. Mol. Biol. 14, 332\u2013340 (2007).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"5142_CR14","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/j.str.2009.08.002","volume":"17","author":"MW Kim","year":"2009","unstructured":"Kim, M. W., Chelliah, Y., Kim, S. W., Otwinowski, Z. & Bezprozvanny, I. Secondary structure of Huntingtin amino-terminal region. Structure 17, 1205\u20131212 (2009).","journal-title":"Structure"},{"key":"5142_CR15","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1021\/jacs.6b10893","volume":"139","author":"M Baias","year":"2017","unstructured":"Baias, M. et al. Structure and Dynamics of the Huntingtin Exon-1 N-Terminus: A Solution NMR Perspective. J. Am. Chem. Soc. 139, 1168\u20131176 (2017).","journal-title":"J. Am. Chem. Soc."},{"key":"5142_CR16","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1016\/j.str.2020.04.008","volume":"28","author":"A Urbanek","year":"2020","unstructured":"Urbanek, A. et al. Flanking Regions Determine the Structure of the Poly-Glutamine in Huntingtin through Mechanisms Common among Glutamine-Rich Human Proteins. Structure 28, 733\u2013746 e5 (2020).","journal-title":"Structure"},{"key":"5142_CR17","doi-asserted-by":"publisher","first-page":"16764","DOI":"10.1073\/pnas.0608175103","volume":"103","author":"SL Crick","year":"2006","unstructured":"Crick, S. L., Jayaraman, M., Frieden, C., Wetzel, R. & Pappu, R. V. Fluorescence correlation spectroscopy shows that monomeric polyglutamine molecules form collapsed structures in aqueous solutions. Proc. Natl Acad. Sci. USA 103, 16764\u201316769 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"5142_CR18","doi-asserted-by":"publisher","first-page":"11884","DOI":"10.1073\/pnas.182276099","volume":"99","author":"S Chen","year":"2002","unstructured":"Chen, S., Ferrone, F. A. & Wetzel, R. Huntington\u2019s disease age-of-onset linked to polyglutamine aggregation nucleation. Proc. Natl Acad. Sci. USA 99, 11884\u201311889 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"5142_CR19","doi-asserted-by":"publisher","first-page":"15400","DOI":"10.1073\/pnas.0501651102","volume":"102","author":"AM Bhattacharyya","year":"2005","unstructured":"Bhattacharyya, A. M., Thakur, A. K. & Wetzel, R. polyglutamine aggregation nucleation: thermodynamics of a highly unfavorable protein folding reaction. Proc. Natl Acad. Sci. USA 102, 15400\u201315405 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"5142_CR20","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.jmb.2008.09.026","volume":"384","author":"A Vitalis","year":"2008","unstructured":"Vitalis, A., Wang, X. & Pappu, R. V. Atomistic simulations of the effects of polyglutamine chain length and solvent quality on conformational equilibria and spontaneous homodimerization. J. Mol. Biol. 384, 279\u2013297 (2008).","journal-title":"J. Mol. Biol."},{"key":"5142_CR21","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1073\/pnas.1521933113","volume":"113","author":"CL Hoop","year":"2016","unstructured":"Hoop, C. L. et al. Huntingtin exon 1 fibrils feature an interdigitated beta-hairpin-based polyglutamine core. Proc. Natl Acad. Sci. USA 113, 1546\u20131551 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"5142_CR22","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1016\/j.molcel.2011.05.013","volume":"43","author":"R Halfmann","year":"2011","unstructured":"Halfmann, R. et al. Opposing effects of glutamine and asparagine govern prion formation by intrinsically disordered proteins. Mol. Cell 43, 72\u201384 (2011).","journal-title":"Mol. Cell"},{"key":"5142_CR23","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1016\/j.cell.2010.11.042","volume":"143","author":"F Fiumara","year":"2010","unstructured":"Fiumara, F., Fioriti, L., Kandel, E. R. & Hendrickson, W. A. Essential role of coiled coils for aggregation and activity of Q\/N-rich prions and PolyQ proteins. Cell 143, 1121\u20131135 (2010).","journal-title":"Cell"},{"key":"5142_CR24","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.jsb.2008.01.016","volume":"163","author":"DA Parry","year":"2008","unstructured":"Parry, D. A., Fraser, R. D. & Squire, J. M. Fifty years of coiled-coils and alpha-helical bundles: a close relationship between sequence and structure. J. Struct. Biol. 163, 258\u2013269 (2008).","journal-title":"J. Struct. Biol."},{"key":"5142_CR25","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.cell.2010.07.020","volume":"142","author":"TJ van Ham","year":"2010","unstructured":"van Ham, T. J. et al. Identification of MOAG-4\/SERF as a regulator of age-related proteotoxicity. Cell 142, 601\u2013612 (2010).","journal-title":"Cell"},{"key":"5142_CR26","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/1753","volume":"20","author":"JM Scharf","year":"1998","unstructured":"Scharf, J. M. et al. Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics. Nat. Genet 20, 83\u201386 (1998).","journal-title":"Nat. Genet"},{"key":"5142_CR27","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/j.celrep.2012.06.012","volume":"2","author":"SF Falsone","year":"2012","unstructured":"Falsone, S. F. et al. SERF Protein Is a Direct Modifier of Amyloid Fiber Assembly. Cell Rep. 2, 358\u2013371 (2012).","journal-title":"Cell Rep."},{"key":"5142_CR28","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1016\/j.jmb.2019.11.014","volume":"432","author":"NH Meyer","year":"2020","unstructured":"Meyer, N. H. et al. Structural Fuzziness of the RNA-Organizing Protein SERF Determines a Toxic Gain-of-interaction. J. Mol. Biol. 432, 930\u2013951 (2020).","journal-title":"J. Mol. Biol."},{"key":"5142_CR29","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1016\/j.jmb.2019.04.031","volume":"431","author":"DA Merle","year":"2019","unstructured":"Merle, D. A. et al. Increased Aggregation Tendency of Alpha-Synuclein in a Fully Disordered Protein Complex. J. Mol. Biol. 431, 2581\u20132598 (2019).","journal-title":"J. Mol. Biol."},{"key":"5142_CR30","doi-asserted-by":"publisher","first-page":"W370","DOI":"10.1093\/nar\/gkv494","volume":"43","author":"NE Hafsa","year":"2015","unstructured":"Hafsa, N. E., Arndt, D. & Wishart, D. S. CSI 3.0: a web server for identifying secondary and super-secondary structure in proteins using NMR chemical shifts. Nucleic Acids Res 43, W370\u2013W377 (2015).","journal-title":"Nucleic Acids Res"},{"key":"5142_CR31","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1016\/S0014-5793(97)01224-6","volume":"416","author":"CE MacPhee","year":"1997","unstructured":"MacPhee, C. E., Perugini, M. A., Sawyer, W. H. & Howlett, G. J. Trifluoroethanol induces the self-association of specific amphipathic peptides. FEBS Lett. 416, 265\u2013268 (1997).","journal-title":"FEBS Lett."},{"key":"5142_CR32","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1021\/bi048564t","volume":"44","author":"R Kunjithapatham","year":"2005","unstructured":"Kunjithapatham, R. et al. Role for the alpha-helix in aberrant protein aggregation. Biochemistry 44, 149\u2013156 (2005).","journal-title":"Biochemistry"},{"key":"5142_CR33","doi-asserted-by":"publisher","first-page":"9679","DOI":"10.1073\/pnas.0812083106","volume":"106","author":"Y Nekooki-Machida","year":"2009","unstructured":"Nekooki-Machida, Y. et al. Distinct conformations of in vitro and in vivo amyloids of huntingtin-exon1 show different cytotoxicity. Proc. Natl Acad. Sci. USA 106, 9679\u20139684 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"5142_CR34","doi-asserted-by":"publisher","first-page":"21647","DOI":"10.1074\/jbc.M109.016923","volume":"284","author":"J Legleiter","year":"2009","unstructured":"Legleiter, J. et al. Monoclonal antibodies recognize distinct conformational epitopes formed by polyglutamine in a mutant huntingtin fragment. J. Biol. Chem. 284, 21647\u201321658 (2009).","journal-title":"J. Biol. Chem."},{"key":"5142_CR35","doi-asserted-by":"publisher","first-page":"34717","DOI":"10.1074\/jbc.M209852200","volume":"278","author":"M Tanaka","year":"2003","unstructured":"Tanaka, M. et al. Expansion of polyglutamine induces the formation of quasi-aggregate in the early stage of protein fibrillization. J. Biol. Chem. 278, 34717\u201334724 (2003).","journal-title":"J. Biol. Chem."},{"key":"5142_CR36","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1126\/science.1079469","volume":"300","author":"R Kayed","year":"2003","unstructured":"Kayed, R. et al. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300, 486\u2013489 (2003).","journal-title":"Science"},{"key":"5142_CR37","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/1750-1326-2-18","volume":"2","author":"R Kayed","year":"2007","unstructured":"Kayed, R. et al. Fibril specific, conformation dependent antibodies recognize a generic epitope common to amyloid fibrils and fibrillar oligomers that is absent in prefibrillar oligomers. Mol. Neurodegener. 2, 18 (2007).","journal-title":"Mol. Neurodegener."},{"key":"5142_CR38","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.sbi.2008.04.008","volume":"18","author":"G Grigoryan","year":"2008","unstructured":"Grigoryan, G. & Keating, A. E. Structural specificity in coiled-coil interactions. Curr. Opin. Struct. Biol. 18, 477\u2013483 (2008).","journal-title":"Curr. Opin. Struct. Biol."},{"key":"5142_CR39","doi-asserted-by":"publisher","first-page":"2664","DOI":"10.1016\/S0021-9258(18)45932-7","volume":"267","author":"NE Zhou","year":"1992","unstructured":"Zhou, N. E., Kay, C. M. & Hodges, R. S. Synthetic model proteins. Positional effects of interchain hydrophobic interactions on stability of two-stranded alpha-helical coiled-coils. J. Biol. Chem. 267, 2664\u20132670 (1992).","journal-title":"J. Biol. Chem."},{"key":"5142_CR40","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.jmb.2003.09.059","volume":"334","author":"N Choy","year":"2003","unstructured":"Choy, N., Raussens, V. & Narayanaswami, V. Inter-molecular coiled-coil formation in human apolipoprotein E C-terminal domain. J. Mol. Biol. 334, 527\u2013539 (2003).","journal-title":"J. Mol. Biol."},{"key":"5142_CR41","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1126\/science.252.5009.1162","volume":"252","author":"A Lupas","year":"1991","unstructured":"Lupas, A., Van Dyke, M. & Stock, J. Predicting coiled coils from protein sequences. Science 252, 1162\u20131164 (1991).","journal-title":"Science"},{"key":"5142_CR42","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1006\/jsbi.1999.4182","volume":"128","author":"DK Chang","year":"1999","unstructured":"Chang, D. K., Cheng, S. F., Trivedi, V. D. & Lin, K. L. Proline affects oligomerization of a coiled coil by inducing a kink in a long helix. J. Struct. Biol. 128, 270\u2013279 (1999).","journal-title":"J. Struct. Biol."},{"key":"5142_CR43","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1038\/nsmb.1570","volume":"16","author":"AK Thakur","year":"2009","unstructured":"Thakur, A. K. et al. Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism. Nat. Struct. Mol. Biol. 16, 380\u2013389 (2009).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"5142_CR44","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.jmb.2005.10.053","volume":"355","author":"A Bhattacharyya","year":"2006","unstructured":"Bhattacharyya, A. et al. Oligoproline effects on polyglutamine conformation and aggregation. J. Mol. Biol. 355, 524\u2013535 (2006).","journal-title":"J. Mol. Biol."},{"key":"5142_CR45","doi-asserted-by":"publisher","first-page":"14610","DOI":"10.1073\/pnas.1301342110","volume":"110","author":"NS Caron","year":"2013","unstructured":"Caron, N. S., Desmond, C. R., Xia, J. & Truant, R. Polyglutamine domain flexibility mediates the proximity between flanking sequences in huntingtin. Proc. Natl Acad. Sci. USA 110, 14610\u201314615 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"5142_CR46","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1074\/jbc.M114.603332","volume":"290","author":"E Monsellier","year":"2015","unstructured":"Monsellier, E., Redeker, V., Ruiz-Arlandis, G., Bousset, L. & Melki, R. Molecular interaction between the chaperone Hsc70 and the N-terminal flank of huntingtin exon 1 modulates aggregation. J. Biol. Chem. 290, 2560\u20132576 (2015).","journal-title":"J. Biol. Chem."},{"key":"5142_CR47","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/nsmb860","volume":"11","author":"JL Wacker","year":"2004","unstructured":"Wacker, J. L., Zareie, M. H., Fong, H., Sarikaya, M. & Muchowski, P. J. Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat. Struct. Mol. Biol. 11, 1215\u20131222 (2004).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"5142_CR48","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1093\/hmg\/ddi071","volume":"14","author":"MA Poirier","year":"2005","unstructured":"Poirier, M. A., Jiang, H. & Ross, C. A. A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: evidence for a compact beta-sheet structure. Hum. Mol. Genet 14, 765\u2013774 (2005).","journal-title":"Hum. Mol. Genet"},{"key":"5142_CR49","doi-asserted-by":"publisher","first-page":"8188","DOI":"10.1074\/jbc.M110.192013","volume":"286","author":"QC Zhang","year":"2011","unstructured":"Zhang, Q. C. et al. A compact beta model of huntingtin toxicity. J. Biol. Chem. 286, 8188\u20138196 (2011).","journal-title":"J. Biol. Chem."},{"key":"5142_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1432-1327.1998.2560001.x","volume":"256","author":"JL Markley","year":"1998","unstructured":"Markley, J. L. et al. Recommendations for the presentation of NMR structures of proteins and nucleic acids\u2013IUPAC-IUBMB-IUPAB Inter-Union Task Group on the standardization of data bases of protein and nucleic acid structures determined by NMR spectroscopy. Eur. J. Biochem 256, 1\u201315 (1998).","journal-title":"Eur. J. Biochem"},{"key":"5142_CR51","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/S0079-6565(98)00025-9","volume":"34","author":"M Sattler","year":"1999","unstructured":"Sattler, M., Schleucher, J. & Griesinger, C. Heteronuclear multidimensional NMR experiments for the structure determination of proteins in solution employing pulsed field gradients. Prog. Nucl. Magn. Reson. Spectrosc. 34, 93\u2013158 (1999).","journal-title":"Prog. Nucl. Magn. Reson. Spectrosc."},{"key":"5142_CR52","doi-asserted-by":"publisher","first-page":"17098","DOI":"10.1021\/jacs.7b08259","volume":"139","author":"S Kumar","year":"2017","unstructured":"Kumar, S., Henning-Knechtel, A., Chehade, I., Magzoub, M. & Hamilton, A. D. Foldamer-Mediated Structural Rearrangement Attenuates Abeta Oligomerization and Cytotoxicity. J. Am. Chem. Soc. 139, 17098\u201317108 (2017).","journal-title":"J. Am. Chem. Soc."},{"key":"5142_CR53","doi-asserted-by":"publisher","first-page":"1954","DOI":"10.1107\/S1600577521009565","volume":"28","author":"DG Liu","year":"2021","unstructured":"Liu, D. G. et al. Optical design and performance of the biological small-angle X-ray scattering beamline at the Taiwan Photon Source. J. Synchrotron Radiat. 28, 1954\u20131965 (2021).","journal-title":"J. Synchrotron Radiat."},{"key":"5142_CR54","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1107\/S1600576722001923","volume":"55","author":"O Shih","year":"2022","unstructured":"Shih, O. et al. Performance of the new biological small- and wide-angle X-ray scattering beamline 13A at the Taiwan Photon Source. J. Appl. Crystallogr. 55, 340\u2013352 (2022).","journal-title":"J. Appl. Crystallogr."},{"key":"5142_CR55","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1107\/S0021889812007662","volume":"45","author":"MV Petoukhov","year":"2012","unstructured":"Petoukhov, M. V. et al. New developments in the ATSAS program package for small-angle scattering data analysis. J. Appl Crystallogr 45, 342\u2013350 (2012).","journal-title":"J. Appl Crystallogr"},{"key":"5142_CR56","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/nmeth.2089","volume":"9","author":"CA Schneider","year":"2012","unstructured":"Schneider, C. A., Rasband, W. S. & Eliceiri, K. W. NIH Image to ImageJ: 25 years of image analysis. Nat. Methods 9, 671\u2013675 (2012).","journal-title":"Nat. Methods"},{"key":"5142_CR57","doi-asserted-by":"publisher","first-page":"6066","DOI":"10.1093\/hmg\/ddv318","volume":"24","author":"FL Chiu","year":"2015","unstructured":"Chiu, F. L. et al. Elucidating the role of the A2A adenosine receptor in neurodegeneration using neurons derived from Huntington\u2019s disease iPSCs. Hum. Mol. Genet 24, 6066\u20136079 (2015).","journal-title":"Hum. Mol. Genet"},{"key":"5142_CR58","doi-asserted-by":"publisher","first-page":"e53487","DOI":"10.1371\/journal.pone.0053487","volume":"8","author":"W Ariesandi","year":"2013","unstructured":"Ariesandi, W., Chang, C. F., Chen, T. E. & Chen, Y. R. Temperature-dependent structural changes of Parkinson\u2019s alpha-synuclein reveal the role of pre-existing oligomers in alpha-synuclein fibrillization. PLoS One 8, e53487 (2013).","journal-title":"PLoS One"},{"key":"5142_CR59","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.1096\/fj.10-175539","volume":"25","author":"CL Ni","year":"2011","unstructured":"Ni, C. L., Shi, H. P., Yu, H. M., Chang, Y. C. & Chen, Y. R. Folding stability of amyloid-beta 40 monomer is an important determinant of the nucleation kinetics in fibrillization. FASEB J. 25, 1390\u20131401 (2011).","journal-title":"FASEB J."}],"updated-by":[{"DOI":"10.1038\/s42003-023-05389-7","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T00:00:00Z","timestamp":1696809600000}},{"DOI":"10.1038\/s42003-024-06302-6","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T00:00:00Z","timestamp":1715990400000}}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-023-05142-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-023-05142-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-023-05142-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,19]],"date-time":"2024-05-19T07:01:54Z","timestamp":1716102114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-023-05142-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,21]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["5142"],"URL":"https:\/\/doi.org\/10.1038\/s42003-023-05142-0","relation":{"correction":[{"id-type":"doi","id":"10.1038\/s42003-024-06302-6","asserted-by":"object"},{"id-type":"doi","id":"10.1038\/s42003-023-05389-7","asserted-by":"object"}]},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,21]]},"assertion":[{"value":"5 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 May 2024","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s42003-024-06302-6","URL":"https:\/\/doi.org\/10.1038\/s42003-024-06302-6","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 October 2023","order":8,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":9,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":10,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s42003-023-05389-7","URL":"https:\/\/doi.org\/10.1038\/s42003-023-05389-7","order":11,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"767"}}