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The N- and C-terminal flanking sequence modules from exon 1 of huntingtin act as gatekeepers, whereby the N-terminal flanking sequence accelerates fibril formation while destabilizing nonfibrillar species, whereas the C-terminal flanking sequence reduces the overall driving force for aggregation. These results provide a mechanistic underpinning for observations regarding naturally occurring sequence contexts as modulators of polyglutamine toxicity.<\/jats:p>","DOI":"10.1073\/pnas.1320626110","type":"journal-article","created":{"date-parts":[[2013,11,26]],"date-time":"2013-11-26T23:29:43Z","timestamp":1385508583000},"page":"20075-20080","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":224,"title":["Unmasking the roles of N- and C-terminal flanking sequences from exon 1 of huntingtin as modulators of polyglutamine aggregation"],"prefix":"10.1073","volume":"110","author":[{"given":"Scott L.","family":"Crick","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiersten M.","family":"Ruff","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130; 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