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

Summary for 3TJ5

• Entry DOI: 10.2210/pdb3tj5/pdb
• Related: 1rkc 2gww 2hsq 2ibf 3TJ6 3rf3 3s90
• Descriptor: Vinculin, Antigenic heat-stable 120 kDa protein, GLYCEROL, ... (4 entities in total)
• Functional Keywords: 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
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane ; Peripheral membrane protein ; Cytoplasmic side : P18206
• Total number of polymer chains: 2
• Total formula weight: 31469.28

Authors

Park, H.,Lee, J.H.,Gouin, E.,Cossart, P.,Izard, T. (deposition date: 2011-08-23, release date: 2011-09-07, Last modification date: 2023-09-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.99 Å)