Crystal structures of fibronectin-binding sites from Staphylococcus aureus FnBPA in complex with fibronectin domains

Staphylococcus aureus can adhere to and invade endothelial cells by binding to the human protein fibronectin (Fn). FnBPA and FnBPB, cell wall-attached proteins from S. aureus, have multiple, intrinsically disordered, high-affinity binding repeats (FnBRs) for Fn. Here, 30 years after the first report of S. aureus/Fn interactions, we present four crystal structures that together comprise the structures of two complete FnBRs, each in complex with four of the N-terminal modules of Fn. Each [approximately equal to] 40-residue FnBR forms antiparallel strands along the triple-stranded [beta]-sheets of four sequential F1 modules ([sup.2-5]F1) with each FnBR/[sup.2-5]F1 interface burying a total surface area of [approximately equal to] 4,300 [[Angstrom].sup.2]. The structures reveal the roles of residues conserved between S. aureus and Streptococcus pyogenes FnBRs and show that there are few linker residues between FnBRs. The ability to form large intermolecular interfaces with relatively few residues has been proposed to be a feature of disordered proteins, and S. aureus/Fn interactions provide an unusual illustration of this efficiency. intrinsic disorder | tandem [beta]-zipper | host-pathogen interaction