The cytotoxic Staphylococcus aureus PSMα3 reveals a cross-α amyloid-like fibril

What's in a fold? Bacterially secreted peptides known as PSMs (phenol-soluble modulins) stimulate inflammatory responses, lyse human cells, and contribute to biofilm structuring. PSMα3 is a virulent 22-residue amyloid peptide secreted by Staphylococcus aureus. Tayeb-Fligelman et al. present a high-resolution structure encompassing the full length of the amyloid's sequence. This structure reveals an unexpected departure from the common amyloid cross-β folded architecture. Instead, PSMα3 forms amphipathic α-helices that are folded to stack perpendicular to the fibril axis into sheets. This unusual cross-α structure was important for fibril toxicity. Science , this issue p. 831