教師資料查詢 | 類別: 期刊論文 | 教師: 蔡旻燁 MIN-YEH TSAI (瀏覽個人網頁)

標題:The Aggregation Free Energy Landscapes of Polyglutamine Repeats
學年105
學期1
出版(發表)日期2016/10/27
作品名稱The Aggregation Free Energy Landscapes of Polyglutamine Repeats
作品名稱(其他語言)
著者Chen, Mingchen; Tsai, Minyeh; Zheng, Weihua; Wolynes, Peter G
單位
出版者
著錄名稱、卷期、頁數J. Am. Chem. Soc., 138(46) 15197
摘要Aggregates of proteins containing polyglutamine (polyQ) repeats are strongly associated with several neurodegenerative diseases. The length of the repeats correlates with the severity of the disease. Previous studies have shown that pure polyQ peptides aggregate by nucleated growth polymerization and that the size of the critical nucleus (n*) decreases from tetrameric to dimeric and monomeric as length increases from Q18 to Q26. Why the critical nucleus size changes with repeat-length has been unclear. Using the associative memory, water-mediated, structure and energy model, we construct the aggregation free energy landscapes for polyQ peptides of different repeat-lengths. These studies show that the monomer of the shorter repeat-length (Q20) prefers an extended conformation and that its aggregation indeed has a trimeric nucleus (n* ∼ 3), while a longer repeat-length monomer (Q30) prefers a β-hairpin conformation which then aggregates in a downhill fashion at 0.1 mM. For an intermediate length peptide (Q26), there is an equal preference for hairpin and extended forms in the monomer which leads to a mixed inhomogeneous nucleation mechanism for fibrils. The predicted changes of monomeric structure and nucleation mechanism are confirmed by studying the aggregation free energy profile for a polyglutamine repeat with site-specific PG mutations that favor the hairpin form, giving results in harmony with experiments on this system.
關鍵字
語言英文(美國)
ISSN0002-7863
期刊性質國外
收錄於SCI;
產學合作
通訊作者
審稿制度
國別美國
公開徵稿
出版型式,電子版,紙本
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