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PDBsum entry 3cyy

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protein ligands Protein-protein interface(s) links
Peptide binding protein PDB id
3cyy
Jmol
Contents
Protein chains
80 a.a. *
Ligands
ARG-PRO-ARG-PRO-
ASP-ASP-LEU-GLU-
ILE
×2
Waters ×77
* Residue conservation analysis
PDB id:
3cyy
Name: Peptide binding protein
Title: The crystal structure of zo-1 pdz2 in complex with the cx43
Structure: Tight junction protein zo-1. Chain: a, b. Fragment: pdz2 domain. Synonym: zonula occludens protein 1, zona occludens protein junction protein 1. Engineered: yes. Mutation: yes. Peptide from gap junction alpha-1 protein. Chain: c, d.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptides
Resolution:
2.40Å     R-factor:   0.217     R-free:   0.254
Authors: L.Pan,M.Zhang
Key ref: J.Chen et al. (2008). Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory connexin43-binding sites. EMBO J, 27, 2113-2123. PubMed id: 18636092 DOI: 10.1038/emboj.2008.138
Date:
27-Apr-08     Release date:   23-Sep-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
No UniProt id for this chain
Struc: 80 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1038/emboj.2008.138 EMBO J 27:2113-2123 (2008)
PubMed id: 18636092  
 
 
Domain-swapped dimerization of ZO-1 PDZ2 generates specific and regulatory connexin43-binding sites.
J.Chen, L.Pan, Z.Wei, Y.Zhao, M.Zhang.
 
  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.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20509869 H.J.Lee, and J.J.Zheng (2010).
PDZ domains and their binding partners: structure, specificity, and modification.
  Cell Commun Signal, 8, 8.  
20086013 S.Chakraborty, S.Mitra, M.M.Falk, S.H.Caplan, M.J.Wheelock, K.R.Johnson, and P.P.Mehta (2010).
E-cadherin differentially regulates the assembly of Connexin43 and Connexin32 into gap junctions in human squamous carcinoma cells.
  J Biol Chem, 285, 10761-10776.  
19274588 E.Y.Kang, M.Ponzio, E.Y.Kang, M.Ponzio, P.P.Gupta, F.Liu, A.Butensky, and D.E.Gutstein (2009).
Identification of Binding Partners for the Cytoplasmic Loop of Connexin43: A Novel Interaction with β-Tubulin.
  Cell Commun Adhes, 15, 397-406.  
  19342771 H.Chen, S.Tong, X.Li, J.Wu, Z.Zhu, L.Niu, and M.Teng (2009).
Structure of the second PDZ domain from human zonula occludens 2.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 327-330.
PDB code: 3e17
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.