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

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 a （Fg a）, 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-Bbp273-598 and Bbp273-598-Fg a561-575 complex at a resolution of 2.03 A and 1.45 A, respectively. Apo-Bbp273-598 contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional DI strand in N2 domain and D1＇ and D2＇ strands in N3 domain. The peptide mapped to the Fg o561-575 bond to Bbp273-sgs 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. BbpAla298-Gly301 in the N2 domain of the Bbp273-598-Fg a561-575 complex, which is a loop in the apo-form, formed a short a-helix to interact tightly with the peptide. In addition, Bbpser547-Glns61 in the N3 domain moved toward the binding groove to make contact directly with the peptide, while BbpAsp338-Gly355 and BbpThr365-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.