3CYY

The crystal structure of ZO-1 PDZ2 in complex with the Cx43 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory connexin43-binding sites

Chen, J.Pan, L.Wei, Z.Zhao, Y.Zhang, M.

(2008) EMBO J 27: 2113-2123

  • DOI: https://doi.org/10.1038/emboj.2008.138
  • Primary Citation of Related Structures:  
    3CYY

  • PubMed Abstract: 

    PDZ domain scaffold proteins are capable of assembling macromolecular protein complexes in diverse cellular processes through PDZ-mediated binding to a short peptide fragment at the carboxyl tail of target proteins. How each PDZ domain specifically recognizes its target protein(s) remains a major conceptual question, as at least a few out of the several hundred PDZ domains in each eukaryotic genome share overlapping binding properties with any given target protein. Here, we show that the domain-swapped dimerization of zonula occludens-1 PDZ2 generates a distinct interface that functions together with the well-separated canonical carboxyl tail-binding pocket in each PDZ unit in binding to connexin43 (Cx43). We further demonstrate that the charge-charge interaction network formed by residues in the PDZ dimer interface and upstream residues of the Cx43 peptide not only provides the unprecedented interaction specificity for the complex but may also function as a phosphorylation-mediated regulatory switch for the dynamics of the Cx43 gap junctions. Finally, we provide evidence that such domain-swapped dimer assembly also occurs in other PDZ domain scaffold proteins. Therefore, our findings present a new paradigm for understanding how some PDZ domain proteins specifically bind to and regulate the functions of their target proteins.


  • Organizational Affiliation

    Department of Biochemistry, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Kowloon, Hong Kong.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tight junction protein ZO-1
A, B
92Homo sapiensMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for Q07157 (Homo sapiens)
Explore Q07157 
Go to UniProtKB:  Q07157
PHAROS:  Q07157
GTEx:  ENSG00000104067 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ07157
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
peptide from Gap junction alpha-1 protein
C, D
9N/AMutation(s): 0 
UniProt
Find proteins for P08050 (Rattus norvegicus)
Explore P08050 
Go to UniProtKB:  P08050
Entity Groups  
UniProt GroupP08050
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.215 
  • R-Value Observed: 0.217 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 41.04α = 90
b = 68.14β = 90
c = 149.69γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata collection
MOSFLMdata reduction
SCALAdata scaling
PHASESphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-09-23
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2021-11-10
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Refinement description