4M00

Crystal structure of the ligand binding region of staphylococcal adhesion SraP

4M00 の概要

• エントリーDOI: 10.2210/pdb4m00/pdb
• 関連するPDBエントリー: 4M01 4M02 4M03
• 関連するBIRD辞書のPRD_ID: PRD_900003
• 分子名称: Serine-rich adhesin for platelets, beta-D-fructofuranose-(2-1)-alpha-D-glucopyranose, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: all beta, adhesion, carbohydrate/sugar binding, cell adhesion
• 由来する生物種: Staphylococcus aureus
• 細胞内の位置: Secreted, cell wall; Peptidoglycan-anchor: Q2FUW1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 57018.79

構造登録者

Yang, Y.H.,Jiang, Y.L.,Zhang, J.,Wang, L.,Chen, Y.,Zhou, C.Z. (登録日: 2013-08-01, 公開日: 2014-06-18, 最終更新日: 2023-11-08)

主引用文献

Yang, Y.H.,Jiang, Y.L.,Zhang, J.,Wang, L.,Bai, X.H.,Zhang, S.J.,Ren, Y.M.,Li, N.,Zhang, Y.H.,Zhang, Z.,Gong, Q.,Mei, Y.,Xue, T.,Zhang, J.R.,Chen, Y.,Zhou, C.Z.
Structural Insights into SraP-Mediated Staphylococcus aureus Adhesion to Host Cells
Plos Pathog., 10:e1004169-e1004169, 2014

PubMed Abstract: 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.

PubMed: 24901708
DOI: 10.1371/journal.ppat.1004169

実験手法

X-RAY DIFFRACTION (2.05 Å)