crystal structures reveal the multi-ligand binding mechanism of staphylococcus aureus clfb晶体结构揭示了金黄色葡萄球菌clfb multi-ligand绑定机制.pdfVIP

Crystal Structures Reveal the Multi-Ligand Binding Mechanism of Staphylococcus aureus ClfB 1,2. 1. 1 3 1 1,4 2 Hua Xiang , Yue Feng , Jiawei Wang , Bao Liu , Yeguang Chen , Lei Liu , Xuming Deng *, Maojun Yang1* 1 Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China, 2 Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China, 3 Department of Vascular Surgery, Peking Union Medical College Hospital, Beijing, China, 4 Department of Chemistry, Tsinghua University, Beijing, China Abstract Staphylococcus aureus (S. aureus) pathogenesis is a complex process involving a diverse array of extracellular and cell wall components. ClfB, an MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family surface protein, described as a fibrinogen-binding clumping factor, is a key determinant of S. aureus nasal colonization, but the molecular basis for ClfB-ligand recognition remains unknown. In this study, we solved the crystal structures of apo-ClfB and its complexes with fibrinogen a (Fg a) and cytokeratin 10 (CK10) peptides. Structural comparison revealed a conserved glycine-serine-rich (GSR) ClfB binding motif (GSSGXGXXG) within the ligands, which was also found in other human proteins such as Engrailed protein, TCF20 and Dermokine proteins. Interaction between Dermokine and ClfB was confirmed by subsequent binding assays. The crystal structure of ClfB complexed with a