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PDBsum entry 4ehp

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protein ligands Protein-protein interface(s) links
Cell adhesion PDB id
4ehp
Jmol
Contents
Protein chains
248 a.a.
93 a.a.
Ligands
ACT ×9
Waters ×82
PDB id:
4ehp
Name: Cell adhesion
Title: Crystal structure of human vinculin head domain (residues 1- complex with alpha-catenin (residues 277-382)
Structure: Vinculin. Chain: a. Fragment: unp residues 1-252. Synonym: metavinculin. Engineered: yes. Catenin alpha-1. Chain: b. Fragment: unp residues 277-382. Synonym: alpha e-catenin, cadherin-associated protein, rena
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: vcl. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: ctnna1.
Resolution:
2.66Å     R-factor:   0.194     R-free:   0.229
Authors: T.Izard,E.S.Rangarajan
Key ref: E.S.Rangarajan and T.Izard (2012). The cytoskeletal protein α-catenin unfurls upon binding to vinculin. J Biol Chem, 287, 18492-18499. PubMed id: 22493458
Date:
03-Apr-12     Release date:   18-Apr-12    
PROCHECK
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 Headers
 References

Protein chain
Pfam   ArchSchema ?
P18206  (VINC_HUMAN) -  Vinculin
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1134 a.a.
248 a.a.
Protein chain
Pfam   ArchSchema ?
P35221  (CTNA1_HUMAN) -  Catenin alpha-1
Seq:
Struc:
 
Seq:
Struc:
906 a.a.
93 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     2 terms  

 

 
J Biol Chem 287:18492-18499 (2012)
PubMed id: 22493458  
 
 
The cytoskeletal protein α-catenin unfurls upon binding to vinculin.
E.S.Rangarajan, T.Izard.
 
  ABSTRACT  
 
Adherens junctions (AJs) are essential for cell-cell contacts, morphogenesis, and the development of all higher eukaryotes. AJs are formed by calcium-dependent homotypic interactions of the ectodomains of single membrane-pass cadherin family receptors. These homotypic interactions in turn promote binding of the intracellular cytoplasmic tail domains of cadherin receptors with β-catenin, a multifunctional protein that plays roles in both transcription and AJs. The cadherin receptor-β-catenin complex binds to the cytoskeletal protein α-catenin, which is essential for both the formation and the stabilization of these junctions. Precisely how α-catenin contributes to the formation and stabilization of AJs is hotly debated, although the latter is thought to involve its interactions with the cytoskeletal protein vinculin. Here we report the crystal structure of the vinculin binding domain (VBD) of α-catenin in complex with the vinculin head domain (Vh1). This structure reveals that α-catenin is in a unique unfurled mode allowing dimer formation when bound to vinculin. Finally, binding studies suggest that vinculin must be in an activated state to bind to α-catenin and that this interaction is stabilized by the formation of a ternary α-catenin-vinculin-F-actin complex, which can be formed via the F-actin binding domain of either protein. We propose a feed-forward model whereby α-catenin-vinculin interactions promote their binding to the actin cytoskeleton to stabilize AJs.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  23292143 E.S.Rangarajan, and T.Izard (2013).
Dimer asymmetry defines α-catenin interactions.
  Nat Struct Mol Biol, 20, 188-193.
PDB code: 4igg
23417122 R.Desai, R.Sarpal, N.Ishiyama, M.Pellikka, M.Ikura, and U.Tepass (2013).
Monomeric α-catenin links cadherin to the actin cytoskeleton.
  Nat Cell Biol, 15, 261-273.  
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.