Backbone Engineering within a Latent β-Hairpin Structure to Design Inhibitors of Polyglutamine Amyloid Formation

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• 作者：Karunakar Kar¹ ; ³ ; Matthew A. Baker² ; ⁴ ; George A. Lengyel² ; ⁵ ; Cody L. Hoop¹ ; ⁶ ; Ravindra Kodali¹ ; In-Ja Byeon¹ ; W. Seth Horne² ; Patrick C.A. van der Wel¹ ; Ronald Wetzel¹ ; ^{rwetzel@pitt.edu}
• 关键词：CP ; cross-polarization ; MAS ; magic angle spinning ; polyQ ; polyglutamine ; ssNMR ; solid-state NMR
• 刊名：Journal of Molecular Biology
• 出版年：2017
• 出版时间：20 January 2017
• 年：2017
• 卷：429
• 期：2
• 页码：308-323
• 全文大小：2430 K
• 卷排序：429

文摘

β-Hairpin formation is implicated in polyQ amyloid nucleation and structure. We prepared polyQ peptides combining β-hairpin motifs with backbone modifications. Peptides with αN-Me-Gln or Pro mutations in the predicted hairpin aggregate poorly. Such mutations at predicted non-H-bonding positions inhibit aggregation in trans. The data clarify assembly mechanisms and provide valuable tools for disease studies.