Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology.

ABSTRACT: Aggregation-prone-motifs (APRs) of proteins are short segments, which - as isolated peptides - form diverse amyloid-like crystals. We introduce two APRs - designed variants of the incretin mimetic Exendin-4 - that both display crystal-phase polymorphism. Crystallographic and spectroscopic analysis revealed that a single amino-acid substitution can greatly reduce topological variability: while LYIQWL can form both parallel and anti-parallel β-sheets, LYIQNL selects only the former. We also found that the parallel/anti-parallel switch of LYIQWL can be induced by simply changing the crystallization temperature. One crystal form of LYIQNL was found to belong to the class 3 topology, an arrangement previously not encountered among proteinogenic systems. We also show that subtle environmental ch

SUBMITTER: Durvanger Z 

PROVIDER: S-EPMC11316126 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature