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PH-controlled stacking direction of the ?-strands in peptide fibrils.

ABSTRACT: Peptides provide a framework for generating functional biopolymers. In this study, the pH-dependent structural changes in the 21-29 fragment peptide of ?₂-microglobulin (?₂m_21-29) during self-aggregation, i.e., the formation of an amyloid fibril, were discussed. The ?-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 ?-sheets existed separately at the intermediate pH (pH?=?7.6-7.7). These results were attributed to the rigidity of the ?-sheets in the fibrils, which prevented the stable hydrogen bonding interactions between the parallel and anti-parallel ?-sheet moieties. This observed pH dependence was ascribed to two phenomena: (i) the pH-dependent collapse of the ?₂m_21-29 fibrils, which consisted of 16?±?3 anti-parallel ?-sheets containing a total of 2000 ?-strands during the deprotonation of the NH₃⁺ group (pK_a?=?8.0) of the ?-strands that occurred within 0.7?±?0.2 strands of each other and (ii) the subsequent formation of the parallel ?-sheets. We propose a framework for a functional biopolymer that could alternate between the two ?-sheet structures in response to pH changes.

SUBMITTER: Tseng WH

PROVIDER: S-EPMC7747703 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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