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The effects of sequence variation in the loop\u2010forming region (referred to as the linker region) on \u03b1S aggregation have yet to be systematically studied. In the study described here, we created and characterized \u03b1S variants containing mutations in the linker regions. Our results indicate that although the physicochemical properties of the linker region, evaluated based on an intrinsic property of a single amino acid, still play a significant role in aggregation, additional factors can also determine aggregation of \u03b1S linker mutants. Our analyses suggest that these factors include a pairwise potential for parallel in\u2010register \u03b2\u2010sheet formation. A linker variant displaying significantly reduced self\u2010aggregation interfered with \u03b1S aggregation by inhibiting the conversion of \u03b1S soluble species to \u03b1S insoluble fibrils. We anticipate that linker mutations could serve as a novel method of creating \u03b1S variants that are aggregationdefective and\/or inhibit \u03b1S aggregation.<\/jats:p>","DOI":"10.1002\/cbic.201100430","type":"journal-article","created":{"date-parts":[[2011,10,13]],"date-time":"2011-10-13T13:23:29Z","timestamp":1318512209000},"page":"2630-2639","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Creation of Aggregation\u2010Defective \u03b1\u2010Synuclein Variants by Engineering the Sequence Connecting \u03b2\u2010Strand\u2010Forming Domains"],"prefix":"10.1002","volume":"12","author":[{"given":"Michael","family":"Hernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Golbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li 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