Crystal structures of Bbp from Staphylococcus aureus reveal the ligand binding mechanism with Fibrinogen α

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 α (Fg α), 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^273-598 and Bbp^273-598-Fg α^561-575 complex at a resolution of 2.03 Å and 1.45 Å, respectively. Apo-Bbp^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 α^561-575 bond to Bbp^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 β-strand G" covering the ligand upon ligand binding. Bbp^{Ala298-Gly301} in the N2 domain of the Bbp^273-598-Fg α^561-575 complex, which is a loop in the apo-form, formed a short α-helix to interact tightly with the peptide. In addition, Bbp^{Ser547-Gln561} in the N3 domain moved toward the binding groove to make contact directly with the peptide, while Bbp^{Asp338-Gly355} and Bbp^{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.