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PDBsum entry 2gdc
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protein Protein-protein interface(s) links
Cell invasion PDB id
2gdc

 

 

 

 

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Contents
Protein chains
238 a.a. *
21 a.a. *
Waters ×14
* Residue conservation analysis
PDB id:
2gdc
Name: Cell invasion
Title: Structure of vinculin vd1 / ipaa560-633 complex
Structure: Vinculin. Chain: a. Fragment: vd1 domain (residues 0-265). Synonym: metavinculin. Engineered: yes. Invasin ipaa. Chain: b. Fragment: c-terminal fragment (residues 560-633). Synonym: 70 kda antigen.
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Gene: vcl, vinc1. Expressed in: escherichia coli. Expression_system_taxid: 562. Shigella flexneri. Organism_taxid: 623. Gene: ipaa.
Biol. unit: Dimer (from PQS)
Resolution:
2.74Å     R-factor:   0.250     R-free:   0.294
Authors: C.Hamiaux,A.Van Eerde,C.Parsot,J.Broos,B.W.Dijkstra
Key ref:
C.Hamiaux et al. (2006). Structural mimicry for vinculin activation by IpaA, a virulence factor of Shigella flexneri. EMBO Rep, 7, 794-799. PubMed id: 16826238 DOI: 10.1038/sj.embor.7400753
Date:
15-Mar-06     Release date:   08-Aug-06    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12003  (VINC_CHICK) -  Vinculin from Gallus gallus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1135 a.a.
238 a.a.
Protein chain
Pfam   ArchSchema ?
P18010  (IPAA_SHIFL) -  Invasin IpaA from Shigella flexneri
Seq:
Struc: 		 
Seq:
Struc: 		633 a.a.
21 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 10 residue positions (black crosses)

 

 
DOI no: 10.1038/sj.embor.7400753 EMBO Rep 7:794-799 (2006)
PubMed id: 16826238  
 
 
Structural mimicry for vinculin activation by IpaA, a virulence factor of Shigella flexneri.
C.Hamiaux, A.van Eerde, C.Parsot, J.Broos, B.W.Dijkstra.
 
  ABSTRACT  
 
Invasion of epithelial cells by Shigella flexneri is characterized by cytoskeletal rearrangements of the host cell membrane, promoting internalization of the bacterium. The bacterial effector IpaA is injected into the epithelial cell by a type III secretion apparatus and recruits vinculin to regulate actin polymerization at the site of entry. We analysed the complex formed between a carboxy-terminal fragment of IpaA (IpaA(560-633)) and the vinculin D1 domain (VD1), both in crystals and in solution. We present evidence that IpaA(560-633) has two alpha-helical vinculin-binding sites that simultaneously bind two VD1 molecules. The interaction of IpaA(560-633) with VD1 is highly similar to the interaction of the endogenous, eukaryotic proteins talin and alpha-actinin with VD1, showing that Shigella uses a structural mimicry strategy to activate vinculin.
 
  Selected figure(s)  
 
Figure 1.
Figure 1 Crystallographic analysis of IpaA[560–633]/VD1 complex. (A) Overall structure of the IpaA[560-633]/VD1 complex and portion of the final [A]-weighted 2F[o]-F[c] electron density map at 1.2 around the Tyr of IpaA at position 2. IpaA (21 residues corresponding to either 18 or 20) is in pink, and VD1 is rainbow-coloured from blue (amino terminus) to red (carboxyl terminus). For IpaA, the positions of the residues according to the consensus sequence are indicated. In the sequence of IpaA[560-633] shown above, 18, 19 and 20 are in red. To the right, the sequence alignment of 18 and 20 is shown, with identical and similar residues in red and blue, respectively. These two helices are aligned with talin VBS1, VBS2 and VBS3 and the VBS consensus sequence. (A), (B), (C) and (D) show the structures of VD1 in complex with IpaA VBS (pink), talin VBS1 (yellow, PDB entry 1SYQ), VBS2 (red, PDB entry 1UH6) and VBS3 (orange, PDB entry 1RKC), respectively. All structures were superimposed using the C atoms of residues 1–250 of VD1 only, using the VD1/VBS1 structure as reference. Part (E) (rotated approximately 90° around the axis of the helix compared with A–D) shows the resulting (unbiased) superimposition of the four VBSs in a stick mode, using the same colour code. Conserved positions (1, 5, 8, 12, 16 and 19) of the consensus sequence are labelled, with the corresponding IpaA residues indicated in parentheses. VD1, vinculin D1 domain; VBS, vinculin-binding site. 		Figure 3.
Figure 3 Gel filtration profiles of IpaA[560-633]/VD1 mixtures at different molar ratios, as indicated. Fractions were collected and analysed by SDS–polyacrylamide gel electrophoresis. VD1, vinculin D1 domain.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO Rep (2006, 7, 794-799) copyright 2006.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
17077085 S.Johnson, P.Roversi, M.Espina, A.Olive, J.E.Deane, S.Birket, T.Field, W.D.Picking, A.J.Blocker, E.E.Galyov, W.L.Picking, and S.M.Lea (2007).
Self-chaperoning of the type III secretion system needle tip proteins IpaD and BipD.
  J Biol Chem, 282, 4035-4044.
PDB codes: 2cmq 2ixr 2j0n 2j0o 2j9t 2jaa
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.  
17074767 H.Chen, D.M.Choudhury, and S.W.Craig (2006).
Coincidence of actin filaments and talin is required to activate vinculin.
  J Biol Chem, 281, 40389-40398.  
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 codes are shown on the right.

 

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