Structural Insights into SraP-Mediated Staphylococcus aureus Adhesion to Host Cells

PLoS Pathogens

Jing-Ren Zhang¹  Juan Zhang²  Xiao-Hui Bai²  Yong-Hui Zhang²  Cong-Zhao Zhou²  Qingguo Gong²  Shi-Jie Zhang²  Yi-Hu Yang²  Lei Wang²  Yong-Liang Jiang²  Ting Xue²  Zhiyong Zhang²  Yide Mei²  Yan-Min Ren²  Yuxing Chen²  Na Li³ 

[1] Center for Infectious Disease Research, School of Medicine, Tsinghua University, Beijing, People's Republic of China;Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei Anhui, People's Republic of China;Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China

关键词: Staphylococcus aureus;    Crystal structure;    Lectins;    Legumes;    Host cells;    Cadherins;    Epithelial cells;    Small-angle scattering;   

DOI  :  10.1371/journal.ppat.1004169

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Staphylococcus aureus, a Gram-positive bacterium causes a number of devastating human diseases, such as infective endocarditis, osteomyelitis, septic arthritis and sepsis. S. aureus SraP, a surface-exposed serine-rich repeat glycoprotein (SRRP), is required for the pathogenesis of human infective endocarditis via its ligand-binding region (BR) adhering to human platelets. It remains unclear how SraP interacts with human host. Here we report the 2.05 Å crystal structure of the BR of SraP, revealing an extended rod-like architecture of four discrete modules. The N-terminal legume lectin-like module specifically binds to N-acetylneuraminic acid. The second module adopts a β-grasp fold similar to Ig-binding proteins, whereas the last two tandem repetitive modules resemble eukaryotic cadherins but differ in calcium coordination pattern. Under the conditions tested, small-angle X-ray scattering and molecular dynamic simulation indicated that the three C-terminal modules function as a relatively rigid stem to extend the N-terminal lectin module outwards. Structure-guided mutagenesis analyses, in addition to a recently identified trisaccharide ligand of SraP, enabled us to elucidate that SraP binding to sialylated receptors promotes S. aureus adhesion to and invasion into host epithelial cells. Our findings have thus provided novel structural and functional insights into the SraP-mediated host-pathogen interaction of S. aureus.

【 授权许可】

CC BY