3TJ5

human vinculin head domain (Vh1, residues 1-258) in complex with the vinculin binding site of the surface cell antigen 4 (sca4-VBS-N; residues 412-434) from Rickettsia rickettsii

3TJ5 の概要

• エントリーDOI: 10.2210/pdb3tj5/pdb
• 関連するPDBエントリー: 1rkc 2gww 2hsq 2ibf 3rf3 3s90 3TJ6
• 分子名称: Vinculin, Antigenic heat-stable 120 kDa protein, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: cytoskeleton, epidemic typhus, sca4, spotted fever, alpha-helix bundle domain, protein-protein interactions, cell adhesion, cytosol, focal adhesion, protein binding-toxin complex, protein binding/toxin
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane ; Peripheral membrane protein ; Cytoplasmic side : P18206
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 31469.28

構造登録者

Park, H.,Lee, J.H.,Gouin, E.,Cossart, P.,Izard, T. (登録日: 2011-08-23, 公開日: 2011-09-07, 最終更新日: 2023-09-13)

主引用文献

Park, H.,Lee, J.H.,Gouin, E.,Cossart, P.,Izard, T.
The rickettsia surface cell antigen 4 applies mimicry to bind to and activate vinculin.
J.Biol.Chem., 286:35096-35103, 2011

PubMed Abstract: Pathogenic Rickettsia species cause high morbidity and mortality, especially R. prowazekii, the causative agent of typhus. Like many intracellular pathogens, Rickettsia exploit the cytoskeleton to enter and spread within the host cell. Here we report that the cell surface antigen sca4 of Rickettsia co-localizes with vinculin in cells at sites of focal adhesions in sca4-transfected cells and that sca4 binds to and activates vinculin through two vinculin binding sites (VBSs) that are conserved across all Rickettsia. Remarkably, this occurs through molecular mimicry of the vinculin-talin interaction that is also seen with the IpaA invasin of the intracellular pathogen Shigella, where binding of these VBSs to the vinculin seven-helix bundle head domain (Vh1) displaces intramolecular interactions with the vinculin tail domain that normally clamp vinculin in an inactive state. Finally, the vinculin·sca4-VBS crystal structures reveal that vinculin adopts a new conformation when bound to the C-terminal VBS of sca4. Collectively, our data define the mechanism by which sca4 activates vinculin and interacts with the actin cytoskeleton, and they suggest important roles for vinculin in Rickettsia pathogenesis.

PubMed: 21841197
DOI: 10.1074/jbc.M111.263855

実験手法

X-RAY DIFFRACTION (1.99 Å)