Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells.
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 en...
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2014-06-01
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doaj-7aeb33bf338845dabb282c4ae29bfb0b2020-11-25T00:12:00ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-06-01106e100416910.1371/journal.ppat.1004169Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells.Yi-Hu YangYong-Liang JiangJuan ZhangLei WangXiao-Hui BaiShi-Jie ZhangYan-Min RenNa LiYong-Hui ZhangZhiyong ZhangQingguo GongYide MeiTing XueJing-Ren ZhangYuxing ChenCong-Zhao ZhouStaphylococcus 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.http://europepmc.org/articles/PMC4047093?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yi-Hu Yang Yong-Liang Jiang Juan Zhang Lei Wang Xiao-Hui Bai Shi-Jie Zhang Yan-Min Ren Na Li Yong-Hui Zhang Zhiyong Zhang Qingguo Gong Yide Mei Ting Xue Jing-Ren Zhang Yuxing Chen Cong-Zhao Zhou |
spellingShingle |
Yi-Hu Yang Yong-Liang Jiang Juan Zhang Lei Wang Xiao-Hui Bai Shi-Jie Zhang Yan-Min Ren Na Li Yong-Hui Zhang Zhiyong Zhang Qingguo Gong Yide Mei Ting Xue Jing-Ren Zhang Yuxing Chen Cong-Zhao Zhou Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells. PLoS Pathogens |
author_facet |
Yi-Hu Yang Yong-Liang Jiang Juan Zhang Lei Wang Xiao-Hui Bai Shi-Jie Zhang Yan-Min Ren Na Li Yong-Hui Zhang Zhiyong Zhang Qingguo Gong Yide Mei Ting Xue Jing-Ren Zhang Yuxing Chen Cong-Zhao Zhou |
author_sort |
Yi-Hu Yang |
title |
Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells. |
title_short |
Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells. |
title_full |
Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells. |
title_fullStr |
Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells. |
title_full_unstemmed |
Structural insights into SraP-mediated Staphylococcus aureus adhesion to host cells. |
title_sort |
structural insights into srap-mediated staphylococcus aureus adhesion to host cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2014-06-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC4047093?pdf=render |
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