PDBsum entry 2hsq

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protein Protein-protein interface(s) links
Cell adhesion, structural protein PDB id
Protein chains
261 a.a. *
23 a.a. *
* Residue conservation analysis
PDB id:
Name: Cell adhesion, structural protein
Title: Human vinculin (head domain, vh1, residues 1-258) in complex with shigella's ipaa vinculin binding site 2 (residues 565-587)
Structure: Vinculin. Chain: a. Synonym: metavinculin. Engineered: yes. Invasin ipaa. Chain: b. Synonym: 70 kda antigen. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: vcl. Expressed in: escherichia coli. Expression_system_taxid: 562. Shigella flexneri. Organism_taxid: 623. Gene: ipaa.
Biol. unit: Dimer (from PQS)
3.97Å     R-factor:   0.289     R-free:   0.316
Authors: T.Izard
Key ref: T.Izard et al. (2006). Shigella applies molecular mimicry to subvert vinculin and invade host cells. J Cell Biol, 175, 465-475. PubMed id: 17088427
22-Jul-06     Release date:   21-Nov-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P18206  (VINC_HUMAN) -  Vinculin
1134 a.a.
261 a.a.
Protein chain
Pfam   ArchSchema ?
Q6XVZ2  (Q6XVZ2_SHIFL) -  IpaA
633 a.a.
23 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     actin cytoskeleton   1 term 
  Biological process     cell adhesion   1 term 
  Biochemical function     structural molecule activity     1 term  


J Cell Biol 175:465-475 (2006)
PubMed id: 17088427  
Shigella applies molecular mimicry to subvert vinculin and invade host cells.
T.Izard, G.Tran Van Nhieu, P.R.Bois.
Shigella flexneri, the causative agent of bacillary dysentery, injects invasin proteins through a type III secretion apparatus upon contacting the host cell, which triggers pathogen internalization. The invasin IpaA is essential for S. flexneri pathogenesis and binds to the cytoskeletal protein vinculin to facilitate host cell entry. We report that IpaA harbors two vinculin-binding sites (VBSs) within its C-terminal domain that bind to and activate vinculin in a mutually exclusive fashion. Only the highest affinity C-terminal IpaA VBS is necessary for efficient entry and cell-cell spread of S. flexneri, whereas the lower affinity VBS appears to contribute to vinculin recruitment at entry foci of the pathogen. Finally, the crystal structures of vinculin in complex with the VBSs of IpaA reveal the mechanism by which IpaA subverts vinculin's functions, where S. flexneri utilizes a remarkable level of molecular mimicry of the talin-vinculin interaction to activate vinculin. Mimicry of vinculin's interactions may therefore be a general mechanism applied by pathogens to infect the host cell.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20722600 J.D.Dunn, and R.H.Valdivia (2010).
Uncivil engineers: Chlamydia, Salmonella and Shigella alter cytoskeleton architecture to invade epithelial cells.
  Future Microbiol, 5, 1219-1232.  
20086044 X.Peng, L.E.Cuff, C.D.Lawton, and K.A.DeMali (2010).
Vinculin regulates cell-surface E-cadherin expression by binding to beta-catenin.
  J Cell Sci, 123, 567-577.  
  19527884 J.E.Galán (2009).
Common themes in the design and function of bacterial effectors.
  Cell Host Microbe, 5, 571-579.  
19165331 J.Mounier, M.R.Popoff, J.Enninga, M.C.Frame, P.J.Sansonetti, and G.T.Van Nhieu (2009).
The IpaC carboxyterminal effector domain mediates Src-dependent actin polymerization during Shigella invasion of epithelial cells.
  PLoS Pathog, 5, e1000271.  
19043403 N.C.Elde, S.J.Child, A.P.Geballe, and H.S.Malik (2009).
Protein kinase R reveals an evolutionary model for defeating viral mimicry.
  Nature, 457, 485-489.  
18202440 G.N.Schroeder, and H.Hilbi (2008).
Molecular pathogenesis of Shigella spp.: controlling host cell signaling, invasion, and death by type III secretion.
  Clin Microbiol Rev, 21, 134-156.  
17932491 G.T.Nhieu, and T.Izard (2007).
Vinculin binding in its closed conformation by a helix addition mechanism.
  EMBO J, 26, 4588-4596.
PDB code: 2ibf
18056416 J.D.Humphries, P.Wang, C.Streuli, B.Geiger, M.J.Humphries, and C.Ballestrem (2007).
Vinculin controls focal adhesion formation by direct interactions with talin and actin.
  J Cell Biol, 179, 1043-1057.  
18074396 R.L.Rich, and D.G.Myszka (2007).
Survey of the year 2006 commercial optical biosensor literature.
  J Mol Recognit, 20, 300-366.  
17662586 S.Mattoo, Y.M.Lee, and J.E.Dixon (2007).
Interactions of bacterial effector proteins with host proteins.
  Curr Opin Immunol, 19, 392-401.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.