Structural Insight Into The Ligand Binding Mechanism Of Bbp As A Member Of Sdr Family

Stapylococcus aureus is the preeminent pathogen of humans and animals that causes a wide range of infections ranging from superficial skin infection such as folliculitis and impetigo to severe infections such as endocarditis, pneumonia, septic arthritis, metastatic infection and osteomyelitis. The virulence of S.aureus infection denpends on the components and products such as surface proteins, toxins, protease, lipase and coagulase. The ahesive ability to the extracellular matrix components is believed to be an important initial step of pathopoiesis, mediated by surface adhesins called MSCRAMMs(Microbial Surface Components Recognizing Adhesive Matrix Molecules).As members of MSCRAMMs, Sdr family proteins are predicted to adopt a similar structural pattern, characterized in the serine-aspartate repeat sequence. A secretary signal sequence locates at N terminus followed by region A and a characterized domain R composed of repeating serine and aspartic acid dipeptides(SD repeats). The C-terminal features that the cell wall-anchoring LPXTG motif(W), a hydrophobic membranespanning domain(M) and a short positively charged cytoplasmic tail(C). In addition, SdrC, SdrD and SdrE have different numbers of B repeats of 110-113 residues inserted between region A and R.The ligand binding site locates at region A which are reported widely.Staphylococcus aureus isolated from bone and joint infections specifically interacts with bone sialoprotein(BSP), a glycoprotein of bone and dentine extracellular matrix, with the corresponding MSCRAMMs called Bbp. The Bbp protein contains an SD-repeat sequence of 154 residues and is thus a member of the Sdr protein family. In our study, we solved the crystal structures of the apo-BbpN2N3 and the complex binding to Fg α. The topology of Bbp was structurally similar with IgG fold. Each of the two domains was made up of two layers of β-sheets packing tightly against each other, while interaction between the two domains was much looser. In the Bbp-ligand, the ligand occupied the groove between N2 and N3 domains and the rearrangement at C-terminus of BbpN2N3 fromed a G′′ strand. We explained the ligand binding mechanism DLL model and complementary characters. Structure comparison of Bbp with SdrG and ClfA showed the conserved residues were playing a significant in recognizing and binding with the ligand.In all, by using structural biology, molecular biology and biochemistry, we have solved the crystal structures of apo-Bbp and Bbp-Fgα complex and analysized the ligand binding character and mechanism. Our studies could be helpful and meaningful for elucidating the pathway of S.aureus infection and allow the development of potent antagonist and antibiotics.