4EHP

Crystal Structure of human vinculin head domain (residues 1-252) in complex with alpha-catenin (residues 277-382)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.66 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

alpha-Catenin unfurls upon binding to vinculin

Rangarajan, E.S.Izard, T.

(2012) J Biol Chem 287: 18492-18499

  • DOI: https://doi.org/10.1074/jbc.M112.351023
  • Primary Citation of Related Structures:  
    4EHP

  • PubMed 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.


  • Organizational Affiliation

    Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida 33458, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Vinculin253Homo sapiensMutation(s): 0 
Gene Names: VCL
UniProt & NIH Common Fund Data Resources
Find proteins for P18206 (Homo sapiens)
Explore P18206 
Go to UniProtKB:  P18206
PHAROS:  P18206
GTEx:  ENSG00000035403 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP18206
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Catenin alpha-1111Homo sapiensMutation(s): 0 
Gene Names: CTNNA1
UniProt & NIH Common Fund Data Resources
Find proteins for P35221 (Homo sapiens)
Explore P35221 
Go to UniProtKB:  P35221
PHAROS:  P35221
GTEx:  ENSG00000044115 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP35221
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.66 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.194 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 57.25α = 90
b = 73.96β = 90
c = 107.43γ = 90
Software Package:
Software NamePurpose
SCALAdata scaling
MOLREPphasing
BUSTER-TNTrefinement
PDB_EXTRACTdata extraction
SERGUIdata collection
XSCALEdata scaling
BUSTERrefinement

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-18
    Type: Initial release
  • Version 1.1: 2013-07-17
    Changes: Database references
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description