Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen [alpha]

Abstract

Bone sialoprotein-binding protein (Bbp), a MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family protein expressed on the surface of Staphylococcus aureus (S. aureus), mediates adherence to fibrinogen [alpha] (Fg [alpha]), a component in the extracellular matrix of the host cell and is important for infection and pathogenesis. In this study, we solved the crystal structures of apo-Bbp^sup 273-598^ and Bbp^sup 273-598^-Fg [alpha]^sup 561-575^ complex at a resolution of 2.03 Å and 1.45 Å, respectively. Apo-Bbp^sup 273-598^ contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional D1 strand in N2 domain and D1' and D2' strands in N3 domain. The peptide mapped to the Fg [alpha]^sup 561-575^ bond to Bbp^sup 273-598^ on the open groove between the N2 and N3 domains. Strikingly, the disordered C-terminus in the apo-form reorganized into a highly-ordered loop and a [beta]-strand G'' covering the ligand upon ligand binding. Bbp^sup Ala298-Gly301^ in the N2 domain of the Bbp^sup 273-598^-Fg [alpha]^sup 561-575^ complex, which is a loop in the apo-form, formed a short [alpha]-helix to interact tightly with the peptide. In addition, Bbp^sup Ser547-Gln561^ in the N3 domain moved toward the binding groove to make contact directly with the peptide, while Bbp^sup Asp338-Gly355^ and Bbp^sup Thr365-Tyr387^ in N2 domain shifted their configurations to stabilize the reorganized C-terminus mainly through strong hydrogen bonds. Altogether, our results revealed the molecular basis for Bbp-ligand interaction and advanced our understanding of S. aureus infection process.