Multistep Conformation Selection in Amyloid Assembly.

• Type of Material: Article
• Authors: Ming-Chien Hsieh, Georgia Institute of Technology; Chen Liang, Emory University; Anil K. Mehta, Emory University; David Lynn, Emory University; Martha A. Grover, Georgia Institute of Technology
• Language: English
• Date: 2017-11-15
• Publisher: American Chemical Society
• Publication Version: Final Published Version
• Copyright Statement: © 2017 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
• Final Published Version (URL): http://dx.doi.org/10.1021/jacs.7b09362
• Title of Journal or Parent Work: Journal of the American Chemical Society
• ISSN: 0002-7863
• Volume: 139
• Issue: 47
• Start Page: 17007
• End Page: 17010
• Grant/Funding Information: The authors thank the McDonnell Foundation (21st Century Science Initiative Grant on Studying Complex Systems, 220020271), the NSF (Grants CHE-1507932 and NSF/DMR-BSF 1610377), and the NIH Alzheimer’s Disease Research Center (P50AG025688) for financial support.
• Research Categories: Chemistry, General; Chemistry, Analytical

Abstract

Defining pathways for amyloid assembly could impact therapeutic strategies for as many as 50 disease states. Here we show that amyloid assembly is subject to different forces regulating nucleation and propagation steps and provide evidence that the more global β-sheet/β-sheet facial complementarity is a critical determinant for amyloid nucleation and structural selection.