TY - JOUR
T1 - The cytotoxic Staphylococcus aureus PSMα3 reveals a cross-α amyloid-like fibril
AU - Tayeb-Fligelman, Einav
AU - Tabachnikov, Orly
AU - Moshe, Asher
AU - Goldshmidt-Tran, Orit
AU - Sawaya, Michael R.
AU - Coquelle, Nicolas
AU - Colletier, Jacques Philippe
AU - Landau, Meytal
PY - 2017/2/24
Y1 - 2017/2/24
N2 - 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 a3 (PSMa3) peptide secreted by Staphylococcus aureus. PSMa3 formed elongated fibrils that shared the morphological and tinctorial characteristics of canonical cross-b eukaryotic amyloids. However, the crystal structure of full-length PSMa3, solved de novo at 1.45 angstrom resolution, revealed a distinctive "cross-α" amyloid-like architecture, in which amphipathic a helices stacked perpendicular to the fibril axis into tight self-associating sheets.The cross-a fibrillation of PSMa3 facilitated cytotoxicity, suggesting that this assembly mode underlies function in S. aureus.
AB - 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 a3 (PSMa3) peptide secreted by Staphylococcus aureus. PSMa3 formed elongated fibrils that shared the morphological and tinctorial characteristics of canonical cross-b eukaryotic amyloids. However, the crystal structure of full-length PSMa3, solved de novo at 1.45 angstrom resolution, revealed a distinctive "cross-α" amyloid-like architecture, in which amphipathic a helices stacked perpendicular to the fibril axis into tight self-associating sheets.The cross-a fibrillation of PSMa3 facilitated cytotoxicity, suggesting that this assembly mode underlies function in S. aureus.
UR - http://www.scopus.com/inward/record.url?scp=85014011098&partnerID=8YFLogxK
U2 - 10.1126/science.aaf4901
DO - 10.1126/science.aaf4901
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AN - SCOPUS:85014011098
SN - 0036-8075
VL - 355
SP - 831
EP - 833
JO - Science
JF - Science
IS - 6327
ER -