资源环境科技发展态势分析平台

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 alpha 3 (PSM alpha 3) peptide secreted by Staphylococcus aureus. PSMa3 formed elongated fibrils that shared the morphological and tinctorial characteristics of canonical cross-beta eukaryotic amyloids. However, the crystal structure of full-length PSMa3, solved de novo at 1.45 angstrom resolution, revealed a distinctive "cross-alpha" amyloid-like architecture, in which amphipathic a helices stacked perpendicular to the fibril axis into tight self-associating sheets. The cross-alpha fibrillation of PSM alpha 3 facilitated cytotoxicity, suggesting that this assembly mode underlies function in S. aureus.