pH-controlled stacking direction of the β-strands in peptide fibrils

• Published in: Scientific reports Vol. 10; no. 1; pp. 22199 - 9
• Main Authors: Tseng, Wei-Hsuan, Chen, Szu-Hua, Hiramatsu, Hirotsugu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 17.12.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 639/638/440/56; 639/638/45/611; Ammonia; Amyloid; Biopolymers; Fibrils; Humanities and Social Sciences; Hydrogen bonding; multidisciplinary; Peptides; pH effects; Rigidity; Science; Science (multidisciplinary); β2 Microglobulin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-79001-x

Peptides provide a framework for generating functional biopolymers. In this study, the pH-dependent structural changes in the 21–29 fragment peptide of β 2 -microglobulin (β 2 m 21–29 ) during self-aggregation, i.e., the formation of an amyloid fibril, were discussed. The β-sheet structures formed during parallel stacking under basic conditions (pH ≥ 7.7) adopted an anti-parallel stacking configuration under acidic conditions (pH ≤ 7.6). The parallel and anti-parallel β-sheets existed separately at the intermediate pH (pH = 7.6–7.7). These results were attributed to the rigidity of the β-sheets in the fibrils, which prevented the stable hydrogen bonding interactions between the parallel and anti-parallel β-sheet moieties. This observed pH dependence was ascribed to two phenomena: (i) the pH-dependent collapse of the β 2 m 21–29 fibrils, which consisted of 16 ± 3 anti-parallel β-sheets containing a total of 2000 β-strands during the deprotonation of the NH 3 + group (p K a  = 8.0) of the β-strands that occurred within 0.7 ± 0.2 strands of each other and (ii) the subsequent formation of the parallel β-sheets. We propose a framework for a functional biopolymer that could alternate between the two β-sheet structures in response to pH changes.