The Cytotoxic PSMα3 Reveals a Cross-α Amyloid-like Fibril

Overview

Journal Science

Specialty Science

Date 2017 Feb 25

PMID 28232575

Citations 122

Authors

Einav Tayeb-Fligelman

Orly Tabachnikov

Asher Moshe

Orit Goldshmidt-Tran

Michael R Sawaya

Nicolas Coquelle

Jacques-Philippe Colletier

Meytal Landau

Affiliations

Soon will be listed here.

Abstract

Amyloids are ordered protein aggregates, found in all kingdoms of life, and are involved in aggregation diseases as well as in physiological activities. In microbes, functional amyloids are often key virulence determinants, yet the structural basis for their activity remains elusive. We determined the fibril structure and function of the highly toxic, 22-residue phenol-soluble modulin α3 (PSMα3) peptide secreted by PSMα3 formed elongated fibrils that shared the morphological and tinctorial characteristics of canonical cross-β eukaryotic amyloids. However, the crystal structure of full-length PSMα3, solved de novo at 1.45 angstrom resolution, revealed a distinctive "cross-α" amyloid-like architecture, in which amphipathic α helices stacked perpendicular to the fibril axis into tight self-associating sheets. The cross-α fibrillation of PSMα3 facilitated cytotoxicity, suggesting that this assembly mode underlies function in .

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