{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T22:42:58Z","timestamp":1778798578951,"version":"3.51.4"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>\n                    Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of the Huntingtin protein (Htt) have been shown to inhibit the aggregation and attenuate the toxicity of mutant Htt proteins\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in various models of Huntington\u2019s disease. Here, we expand on these studies by investigating the effect of methionine eight oxidation (oxM8) and its crosstalk with lysine 6 acetylation (AcK6) or threonine 3 phosphorylation (pT3) on the aggregation of mutant Httex1 (mHttex1). We show that M8 oxidation delays but does not inhibit the aggregation and has no effect on the final morphologies of mHttex1aggregates. The presence of both oxM8 and AcK6 resulted in dramatic inhibition of Httex1 fibrillization. Circular dichroism spectroscopy and molecular dynamics simulation studies show that PTMs that lower the mHttex1 aggregation rate (oxM8, AcK6\/oxM8, pT3, pT3\/oxM8, and pS13) result in increased population of a short N-terminal helix (first eight residues) in Nt17 or decreased abundance of other helical forms, including long helix and short C-terminal helix. PTMs that did not alter the aggregation rate (AcK6) of mHttex1 exhibit a similar distribution of helical conformation as the unmodified peptides. These results show that the relative abundance of N- vs. C-terminal helical conformations and long helices, rather than the overall helicity of Nt17, better explains the effect of different Nt17 PTMs on mHttex1; thus, explaining the lack of correlation between the effect of PTMs on the overall helicity of Nt17 and mHttex1 aggregation\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Taken together, our results provide novel structural insight into the differential effects of single PTMs and crosstalk between different PTMs in regulating mHttex1 aggregation.\n                  <\/jats:p>","DOI":"10.3389\/fmolb.2021.686086","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T07:00:51Z","timestamp":1627282851000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Investigating Crosstalk Among PTMs Provides Novel Insight Into the Structural Basis Underlying the Differential Effects of Nt17 PTMs on Mutant Httex1 Aggregation"],"prefix":"10.3389","volume":"8","author":[{"given":"Anass","family":"Chiki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhidian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kolla","family":"Rajasekhar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano A.","family":"Abriata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman","family":"Rostami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucien F.","family":"Krapp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Driss","family":"Boudeffa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Dal Peraro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hilal A.","family":"Lashuel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High Performance Molecular Simulations through Multi-Level Parallelism from Laptops to Supercomputers","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"B2","doi-asserted-by":"publisher","first-page":"29427","DOI":"10.1074\/jbc.m109.013193","article-title":"Phosphorylation of Threonine 3","volume":"284","author":"Aiken","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1128\/mcb.01199-09","article-title":"The Chaperone-like Protein HYPK Acts Together with NatA in Cotranslational N-Terminal Acetylation and Prevention of Huntingtin Aggregation","volume":"30","author":"Arnesen","year":"2010","journal-title":"Mol. Cel Biol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1093\/hmg\/ddu504","article-title":"Comparative Study of Naturally Occurring Huntingtin Fragments in Drosophila Points to Exon 1 as the Most Pathogenic Species in Huntington's Disease","volume":"24","author":"Barbaro","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.bbapap.2007.06.016","article-title":"Oxidation Reduces the Fibrillation but Not the Neurotoxicity of the Prion Peptide PrP106-126","volume":"1774","author":"Bergstr\u00f6m","year":"2007","journal-title":"Biochim. Biophys. Acta (Bba) - Proteins Proteomics"},{"key":"B6","doi-asserted-by":"publisher","first-page":"E10809","DOI":"10.1073\/pnas.1705372114","article-title":"Phosphorylation of Huntingtin at Residue T3 Is Decreased in Huntington's Disease and Modulates Mutant Huntingtin Protein Conformation","volume":"114","author":"Cariulo","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"B7","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1021\/jacs.8b11441","article-title":"TiO2 Nanoparticles Catalyze Oxidation of Huntingtin Exon 1-derived Peptides Impeding Aggregation: A Quantitative NMR Study of Binding and Kinetics","volume":"141","author":"Ceccon","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"B8","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.bbrc.2007.05.093","article-title":"Increased Oxidative Damage and Mitochondrial Abnormalities in the Peripheral Blood of Huntington's Disease Patients","volume":"359","author":"Chen","year":"2007","journal-title":"Biochem. biophysical Res. Commun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"5202","DOI":"10.1002\/anie.201611750","article-title":"Mutant Exon1 Huntingtin Aggregation Is Regulated by T3 Phosphorylation-Induced Structural Changes and Crosstalk between T3 Phosphorylation and Acetylation at K6","volume":"56","author":"Chiki","year":"2017","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"B10","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1002\/cbic.202000508","article-title":"Site-specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases","volume":"22","author":"Chiki","year":"2020","journal-title":"Chembiochem"},{"key":"B11","doi-asserted-by":"publisher","first-page":"18540","DOI":"10.1074\/jbc.ra118.004621","article-title":"N-terminal Huntingtin (Htt) Phosphorylation Is a Molecular Switch Regulating Htt Aggregation, Helical Conformation, Internalization, and Nuclear Targeting","volume":"293","author":"DeGuire","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain","volume":"277","author":"DiFiglia","year":"1997","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3937","DOI":"10.1093\/hmg\/ddw234","article-title":"Huntingtin N17 Domain Is a Reactive Oxygen Species Sensor Regulating Huntingtin Phosphorylation and Localization","volume":"25","author":"DiGiovanni","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.bbrep.2015.07.017","article-title":"Effect of Methionine-35 Oxidation on the Aggregation of Amyloid-\u03b2 Peptide","volume":"3","author":"Friedemann","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/prot.340230412","article-title":"Knowledge-based Protein Secondary Structure Assignment","volume":"23","author":"Frishman","year":"1995","journal-title":"Proteins"},{"key":"B16","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3791\/253","article-title":"Transformation of Plasmid DNA into E. coli Using the Heat Shock Method","author":"Froger","year":"2007","journal-title":"J. Vis. Exp."},{"key":"B17","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.cell.2004.06.018","article-title":"Huntingtin Controls Neurotrophic Support and Survival of Neurons by Enhancing BDNF Vesicular Transport along Microtubules","volume":"118","author":"Gauthier","year":"2004","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1002\/jcc.21536","article-title":"Force Field Parameters for the Simulation of Modified Histone Tails","volume":"31","author":"Grauffel","year":"2010","journal-title":"J. Comput. Chem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/j.bbapap.2016.04.009","article-title":"Methionine Oxidation Reduces Lag-Times for Amyloid-\u0392(1-40) Fiber Formation but Generates Highly Fragmented Fibers","volume":"1864","author":"Gu","year":"2016","journal-title":"Biochim. Biophys. Acta (Bba) - Proteins Proteomics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.neuron.2009.11.020","article-title":"Serines 13 and 16 Are Critical Determinants of Full-Length Human Mutant Huntingtin Induced Disease Pathogenesis in HD Mice","volume":"64","author":"Gu","year":"2009","journal-title":"Neuron"},{"key":"B21","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/306234a0","article-title":"A Polymorphic DNA Marker Genetically Linked to Huntington's Disease","volume":"306","author":"Gusella","year":"1983","journal-title":"Nature"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e104671","DOI":"10.15252\/embj.2020104671","article-title":"TBK1 Phosphorylates Mutant Huntingtin and Suppresses its Aggregation and Toxicity in Huntington's Disease Models","volume":"39","author":"Hegde","year":"2020","journal-title":"EMBO J."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1002\/(sici)1096-987x(199709)18:12<1463:aid-jcc4>3.0.co;2-h","article-title":"LINCS: a Linear Constraint Solver for Molecular Simulations","volume":"18","author":"Hess","year":"1997","journal-title":"J. Comput. Chem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/s0896-6273(00)80764-3","article-title":"A YAC Mouse Model for Huntington's Disease with Full-Length Mutant Huntingtin, Cytoplasmic Toxicity, and Selective Striatal Neurodegeneration","volume":"23","author":"Hodgson","year":"1999","journal-title":"Neuron"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1469-7793.2001.0001j.x","article-title":"Regulation of Cell Function by Methionine Oxidation and Reduction","volume":"531","author":"Hoshi","year":"2001","journal-title":"J. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: an Improved Force Field for Folded and Intrinsically Disordered Proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"key":"B27","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. graphics"},{"key":"B28","article-title":"On Chorea","volume-title":"Medical and Surgical Reporter","author":"Huntington","year":"1872"},{"key":"B29","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.ymeth.2011.01.001","article-title":"Assays for Studying Nucleated Aggregation of Polyglutamine Proteins","volume":"53","author":"Jayaraman","year":"2011","journal-title":"Methods"},{"key":"B30","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.cell.2009.03.018","article-title":"Acetylation Targets Mutant Huntingtin to Autophagosomes for Degradation","volume":"137","author":"Jeong","year":"2009","journal-title":"Cell"},{"key":"B31","doi-asserted-by":"publisher","first-page":"4485","DOI":"10.1002\/jps.21746","article-title":"Methionine, Tryptophan, and Histidine Oxidation in a Model Protein, PTH: Mechanisms and Stabilization","volume":"98","author":"Ji","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1097\/wnr.0b013e3280b07c21","article-title":"Attenuated Amyloid-\u03b2 Aggregation and Neurotoxicity Owing to Methionine Oxidation","volume":"18","author":"Johansson","year":"2007","journal-title":"Neuroreport"},{"key":"B33","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of Simple Potential Functions for Simulating Liquid Water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"B34","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1006\/abio.1996.0131","article-title":"The Use of T-Butyl Hydroperoxide as a Probe for Methionine Oxidation in Proteins","volume":"236","author":"Keck","year":"1996","journal-title":"Anal. Biochem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1056\/nejm199405193302001","article-title":"A Worldwide Study of the Huntington's Disease Mutation: The Sensitivity and Specificity of Measuring CAG Repeats","volume":"330","author":"Kremer","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1214\/aoms\/1177729694","article-title":"On Information and Sufficiency","volume":"22","author":"Kullback","year":"1951","journal-title":"Ann. Math. Statist."},{"key":"B37","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3233\/jhd-160205","article-title":"Oxidative Stress and Huntington's Disease: The Good, the Bad, and the Ugly","volume":"5","author":"Kumar","year":"2016","journal-title":"Jhd"},{"key":"B38","doi-asserted-by":"publisher","first-page":"8808","DOI":"10.1074\/jbc.m109.075028","article-title":"Proteolysis of Mutant Huntingtin Produces an Exon 1 Fragment that Accumulates as an Aggregated Protein in Neuronal Nuclei in Huntington Disease","volume":"285","author":"Landles","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B39","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/bit.260480511","article-title":"Chemical Instability of Protein Pharmaceuticals: Mechanisms of Oxidation and Strategies for Stabilization","volume":"48","author":"Li","year":"1995","journal-title":"Biotechnol. Bioeng."},{"key":"B40","doi-asserted-by":"publisher","first-page":"61a","DOI":"10.1016\/j.bpj.2019.11.508","article-title":"Methionine Oxidation Alters the Mechanism of A\u03b2 Interaction with DMPC Bilayers","volume":"118","author":"Lockhart","year":"2020","journal-title":"Biophysical J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/s1097-2765(02)00602-0","article-title":"Proteases Acting on Mutant Huntingtin Generate Cleaved Products that Differentially Build up Cytoplasmic and Nuclear Inclusions","volume":"10","author":"Lunkes","year":"2002","journal-title":"Mol. Cel"},{"key":"B42","doi-asserted-by":"publisher","first-page":"25134","DOI":"10.1074\/jbc.m110.160440","article-title":"Chemical Modifications in Therapeutic Protein Aggregates Generated under Different Stress Conditions","volume":"286","author":"Luo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B43","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-e","article-title":"A Novel Gene Containing a Trinucleotide Repeat that Is Expanded and Unstable on Huntington's Disease Chromosomes","volume":"72","author":"MacDonald","year":"1993","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/s0092-8674(00)81369-0","article-title":"Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic Mice","volume":"87","author":"Mangiarini","year":"1996","journal-title":"Cell"},{"key":"B45","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1212\/wnl.54.2.452","article-title":"Rate of Functional Decline in Huntington's Disease","volume":"54","author":"Marder","year":"2000","journal-title":"Neurology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1038\/ng0298-150","article-title":"Length of Huntingtin and its Polyglutamine Tract Influences Localization and Frequency of Intracellular Aggregates","volume":"18","author":"Martindale","year":"1998","journal-title":"Nat. Genet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"W315","DOI":"10.1093\/nar\/gky497","article-title":"BeStSel: a Web Server for Accurate Protein Secondary Structure Prediction and Fold Recognition from the Circular Dichroism Spectra","volume":"46","author":"Micsonai","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B48","doi-asserted-by":"publisher","first-page":"34764","DOI":"10.1074\/jbc.m112.387035","article-title":"Post-aggregation Oxidation of Mutant Huntingtin Controls the Interactions between Aggregates","volume":"287","author":"Mitomi","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1002\/prot.20310","article-title":"Energy Landscape of a Small Peptide Revealed by Dihedral Angle Principal Component Analysis","volume":"58","author":"Mu","year":"2005","journal-title":"Proteins"},{"key":"B50","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1080\/00268978400101201","article-title":"A Molecular Dynamics Method for Simulations in the Canonical Ensemble","volume":"52","author":"Nos\u00e9","year":"1984","journal-title":"Mol. Phys."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1080\/00268978300102851","article-title":"Constant Pressure Molecular Dynamics for Molecular Systems","volume":"50","author":"Nos\u00e9","year":"1983","journal-title":"Mol. Phys."},{"key":"B52","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/s0076-6879(06)13003-7","article-title":"Kinetics and Thermodynamics of Amyloid Assembly Using a High\u2010Performance Liquid Chromatography-Based Sedimentation Assay","volume":"413","author":"O'Nuallain","year":"2006","journal-title":"Methods Enzymol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/s0076-6879(06)13003-7","article-title":"Kinetics and Thermodynamics of Amyloid Assembly Using a High\u2010Performance Liquid Chromatography-Based Sedimentation Assay","volume":"413","author":"O'Nuallain","year":"2006","journal-title":"Amyloid, Prions, and Other Protein Aggregates, Pt C"},{"key":"B54","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.celrep.2013.06.034","article-title":"SUMO-2 and PIAS1 Modulate Insoluble Mutant Huntingtin Protein Accumulation","volume":"4","author":"O\u2019Rourke","year":"2013","journal-title":"Cel Rep."},{"key":"B55","doi-asserted-by":"publisher","first-page":"7182","DOI":"10.1063\/1.328693","article-title":"Polymorphic Transitions in Single Crystals: A New Molecular Dynamics Method","volume":"52","author":"Parrinello","year":"1981","journal-title":"J. Appl. Phys."},{"key":"B56","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3389\/fmolb.2019.00095","article-title":"The Role of post-translational Modifications on the Energy Landscape of Huntingtin N-Terminus","volume":"6","author":"Pastore","year":"2019","journal-title":"Front. Mol. biosciences"},{"key":"B57","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1136\/jnnp.71.3.310","article-title":"Neuropsychiatric Aspects of Huntington's Disease","volume":"71","author":"Paulsen","year":"2001","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B58","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/s0304-3940(99)00578-9","article-title":"Oxidative Damage to Mitochondrial DNA in Huntington's Disease Parietal Cortex","volume":"272","author":"Polidori","year":"1999","journal-title":"Neurosci. Lett."},{"key":"B59","doi-asserted-by":"publisher","first-page":"57506","DOI":"10.3791\/57506","article-title":"Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy","author":"Reif","year":"2018","journal-title":"J. Vis. Exp."},{"key":"B60","doi-asserted-by":"publisher","first-page":"5733","DOI":"10.1073\/pnas.85.15.5733","article-title":"Differential Loss of Striatal Projection Neurons in Huntington Disease","volume":"85","author":"Reiner","year":"1988","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1212\/01.wnl.0000065888.88988.6e","article-title":"Evidence for More Widespread Cerebral Pathology in Early HD: an MRI-Based Morphometric Analysis","volume":"60","author":"Rosas","year":"2003","journal-title":"Neurology"},{"key":"B62","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/s1474-4422(10)70245-3","article-title":"Huntington's Disease: from Molecular Pathogenesis to Clinical Treatment","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1073\/pnas.1221891110","article-title":"Aberrant Splicing of HTT Generates the Pathogenic Exon 1 Protein in Huntington Disease","volume":"110","author":"Sathasivam","year":"2013","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B64","doi-asserted-by":"publisher","first-page":"4604","DOI":"10.1073\/pnas.96.8.4604","article-title":"Self-assembly of Polyglutamine-Containing Huntingtin Fragments into Amyloid-like Fibrils: Implications for Huntington's Disease Pathology","volume":"96","author":"Scherzinger","year":"1999","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1021\/acschemneuro.9b00509","article-title":"SUMOylation Prevents Huntingtin Fibrillization and Localization onto Lipid Membranes","volume":"11","author":"Sedighi","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/ng0893-393","article-title":"Relationship between Trinucleotide Repeat Expansion and Phenotypic Variation in Huntington's Disease","volume":"4","author":"Snell","year":"1993","journal-title":"Nat. Genet."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1915","DOI":"10.1074\/jbc.ra117.001440","article-title":"High-mobility Group Box 1 Links Sensing of Reactive Oxygen Species by Huntingtin to its Nuclear Entry","volume":"294","author":"Son","year":"2019","journal-title":"J. Biol. Chem."},{"key":"B68","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1126\/science.1092194","article-title":"SUMO Modification of Huntingtin and Huntington's Disease Pathology","volume":"304","author":"Steffan","year":"2004","journal-title":"Science"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1083\/jcb.200909067","article-title":"IKK Phosphorylates Huntingtin and Targets it for Degradation by the Proteasome and Lysosome","volume":"187","author":"Thompson","year":"2009","journal-title":"J. Cel Biol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"34979","DOI":"10.1074\/jbc.m112.374504","article-title":"The Methionine-Aromatic Motif Plays a Unique Role in Stabilizing Protein Structure","volume":"287","author":"Valley","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"12074","DOI":"10.1074\/jbc.m116.713982","article-title":"An Intein-Based Strategy for the Production of Tag-free Huntingtin Exon 1 Proteins Enables New Insights into the Polyglutamine Dependence of Httex1 Aggregation and Fibril Formation","volume":"291","author":"Vieweg","year":"2016","journal-title":"J. Biol. Chem."},{"key":"B72","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1093\/hmg\/ddi165","article-title":"Huntingtin Phosphorylation on Serine 421 Is Significantly Reduced in the Striatum and by Polyglutamine Expansion In Vivo","volume":"14","author":"Warby","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"B73","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1002\/jps.20726","article-title":"Evaluation of Hydroperoxides in Common Pharmaceutical Excipients","volume":"96","author":"Wasylaschuk","year":"2007","journal-title":"J. Pharm. Sci."},{"key":"B74","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3389\/fmolb.2019.00095","article-title":"The Role of Post-translational Modifications on the Energy Landscape of Huntingtin N-Terminus","volume":"6","author":"Yalinca","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1038\/nn1702","article-title":"Palmitoylation of Huntingtin by HIP14is Essential for its Trafficking and Function","volume":"9","author":"Yanai","year":"2006","journal-title":"Nat. Neurosci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.bbadis.2009.12.004","article-title":"Methionine Oxidation Stabilizes Non-toxic Oligomers of \u03b1-synuclein through Strengthening the Auto-Inhibitory Intra-molecular Long-Range Interactions","volume":"1802","author":"Zhou","year":"2010","journal-title":"Biochim. Biophys. Acta (Bba) - Mol. Basis Dis."}],"container-title":["Frontiers in Molecular Biosciences"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2021.686086\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T07:00:56Z","timestamp":1627282856000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmolb.2021.686086\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,26]]},"references-count":76,"alternative-id":["10.3389\/fmolb.2021.686086"],"URL":"https:\/\/doi.org\/10.3389\/fmolb.2021.686086","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.02.21.432155","asserted-by":"object"}]},"ISSN":["2296-889X"],"issn-type":[{"value":"2296-889X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,26]]},"article-number":"686086"}}