pH-controlled stacking direction of the ß-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 ß2-microglobulin (ß2m21-29) during self-aggregation, i.e., the formation of an amyloid fibril, were discussed. The ß-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 ß-sheets existed separately at the intermediate pH (pH = 7.6-7.7). These results were attributed to the rigidity of the ß-sheets in the fibrils, which prevented the stable hydrogen bonding interactions between the parallel and anti-parallel ß-sheet moieties. This observed pH dependence was ascribed to two phenomena (i) the pH-dependent collapse of the ß2m21-29 fibrils, which consisted of 16 ± 3 anti-parallel ß-sheets containing a total of 2000 ß-strands during the deprotonation of the NH3+ group (pKa = 8.0) of the ß-strands that occurred within 0.7 ± 0.2 strands of each other and (ii) the subsequent formation of the parallel ß-sheets. We propose a framework for a functional biopolymer that could alternate between the two ß-sheet structures in response to pH changes.