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Amyloid evolution: antiparallel replaced by parallel

journal contribution
posted on 2025-03-17, 05:00 authored by AAH Zanjani, Nicholas ReynoldsNicholas Reynolds, A Zhang, T Schilling, R Mezzenga, JT Berryman
Several atomic structures have now been found for micrometer-scale amyloid fibrils or elongated microcrystals using a range of methods, including NMR, electron microscopy, and X-ray crystallography, with parallel β-sheet appearing as the most common secondary structure. The etiology of amyloid disease, however, indicates nanometer-scale assemblies of only tens of peptides as significant agents of cytotoxicity and contagion. By combining solution X-ray with molecular dynamics, we show that antiparallel structure dominates at the first stages of aggregation for a specific set of peptides, being replaced by parallel at large length scales only. This divergence in structure between small and large amyloid aggregates should inform future design of molecular therapeutics against nucleation or intercellular transmission of amyloid. Calculations and an overview from the literature argue that antiparallel order should be the first appearance of structure in many or most amyloid aggregation processes, regardless of the endpoint. Exceptions to this finding should exist, depending inevitably on the sequence and on solution conditions.

History

Publication Date

2020-05-19

Journal

Biophysical Journal

Volume

118

Issue

10

Pagination

11p. (p. 2526-2536)

Publisher

Cell Press

ISSN

0006-3495

Rights Statement

© 2020 Biophysical Society. This is an open access article under the CC BY license: http://creativecommons.org/licenses/by/4.0/

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