Crystal Structures Reveal the Multi-Ligand Binding Mechanism of Staphylococcus aureus ClfB

PLoS Pathogens

Maojun Yang¹  Yeguang Chen²  Yue Feng³  Lei Liu⁴  Hua Xiang⁴  Bao Liu⁴  Xuming Deng⁴  Jiawei Wang⁴ 

[1] Department of Chemistry, Tsinghua University, Beijing, China;Department of Vascular Surgery, Peking Union Medical College Hospital, Beijing, China;Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China;Key Laboratory for Protein Sciences of Ministry of Education, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

关键词: Staphylococcus aureus;    Crystal structure;    Hydrogen bonding;    Sequence motif analysis;    Staphylococcal infection;    Opportunistic infections;    Fibrinogen;    Inflammatory diseases;   

DOI  :  10.1371/journal.ppat.1002751

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 α (Fg α) 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 15-residue peptide derived from Dermokine revealed the same peptide binding mode of ClfB as identified in the crystal structures of ClfB-Fg α and ClfB-CK10. The results presented here highlight the multi-ligand binding property of ClfB, which is very distinct from other characterized MSCRAMMs to-date. The adherence of multiple peptides carrying the GSR motif into the same pocket in ClfB is reminiscent of MHC molecules. Our results provide a template for the identification of other molecules targeted by S. aureus during its colonization and infection. We propose that other MSCRAMMs like ClfA and SdrG also possess multi-ligand binding properties.

【 授权许可】

CC BY