title: The cytotoxicStaphylococcus aureusPSMα3 reveals a cross-α amyloid-like fibril.
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 byStaphylococcus aureusPSMα3 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 inS. aureus.
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
authors.forename: Einav
authors.identifier: 0000-0001-9318-5400
authors.initials: E
authors.lastname: Tayeb-Fligelman
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
authors.forename: Orly
authors.identifier: 0000-0001-8372-7392
authors.initials: O
authors.lastname: Tabachnikov
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
authors.forename: Asher
authors.initials: A
authors.lastname: Moshe
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel.
authors.forename: Orit
authors.identifier: 0000-0002-5117-134X
authors.initials: O
authors.lastname: Goldshmidt-Tran
authors.affiliation: Department of Biological Chemistry, Department of Chemistry and Biochemistry, and Howard Hughes Medical Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Michael R
authors.identifier: 0000-0003-0874-9043
authors.initials: MR
authors.lastname: Sawaya
authors.affiliation: Institut de Biologie Structurale (IBS), Université Grenoble Alpes-CEA-CNRS UMR 5075, Grenoble 38044, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coquelle
authors.affiliation: Institut de Biologie Structurale (IBS), Université Grenoble Alpes-CEA-CNRS UMR 5075, Grenoble 38044, France.
authors.forename: Jacques-Philippe
authors.initials: JP
authors.lastname: Colletier
authors.affiliation: Department of Biology, Technion-Israel Institute of Technology, Haifa 3200003, Israel. mlandau@technion.ac.il.
authors.forename: Meytal
authors.identifier: 0000-0002-1743-3430
authors.initials: M
authors.lastname: Landau
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism*; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D006801:Humans; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity*; D013601:T-Lymphocytes / Q000382:microbiology
chemical_list: D000682:Amyloid; D001427:Bacterial Toxins; C025971:staphylococcal delta toxin