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PDBsum entry 2qt5

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protein ligands Protein-protein interface(s) links
Peptide binding protein PDB id
2qt5
Jmol
Contents
Protein chains
194 a.a. *
Ligands
GLY-THR-GLU-VAL ×2
EDO ×2
ACY ×2
Waters ×212
* Residue conservation analysis
PDB id:
2qt5
Name: Peptide binding protein
Title: Crystal structure of grip1 pdz12 in complex with the fras1 peptide
Structure: Glutamate receptor-interacting protein 1. Chain: a, b. Fragment: pdz12. Synonym: grip1 protein, ampa receptor-interacting protein grip1. Engineered: yes. (Asn)(asn)(leu)(gln)(asp)(gly)(thr)(glu)(val). Chain: x, y. Synonym: fras1.
Source: Rattus norvegicus. Rat. Gene: grip1. Expressed in: escherichia coli. Synthetic: yes. Other_details: commercially synthesized
Resolution:
2.30Å     R-factor:   0.202     R-free:   0.247
Authors: J.Long,Z.Wei,W.Feng,Y.Zhao,M.Zhang
Key ref:
J.Long et al. (2008). Supramodular nature of GRIP1 revealed by the structure of its PDZ12 tandem in complex with the carboxyl tail of Fras1. J Mol Biol, 375, 1457-1468. PubMed id: 18155042 DOI: 10.1016/j.jmb.2007.11.088
Date:
01-Aug-07     Release date:   03-Jun-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P97879  (GRIP1_RAT) -  Glutamate receptor-interacting protein 1
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1112 a.a.
194 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     dendrite development   1 term 
  Biochemical function     receptor signaling complex scaffold activity     1 term  

 

 
DOI no: 10.1016/j.jmb.2007.11.088 J Mol Biol 375:1457-1468 (2008)
PubMed id: 18155042  
 
 
Supramodular nature of GRIP1 revealed by the structure of its PDZ12 tandem in complex with the carboxyl tail of Fras1.
J.Long, Z.Wei, W.Feng, C.Yu, Y.X.Zhao, M.Zhang.
 
  ABSTRACT  
 
The scaffold protein GRIP1 (glutamate receptor interacting protein 1) binds to and regulates both the trafficking and membrane organization of a large number of transmembrane proteins. Mutation of GRIP1 in mice displays essentially the same phenotype of the mutations of Fras1 or Frem2, which are the animal models of the human genetic disorder Fraser syndrome. However, the molecular basis governing the interaction between GRIP1 and Fras1/Frem2 is unknown. Here, we show that interaction between Fras1 and GRIP1 requires the first two PDZ domains (PDZ1 and PDZ2) to be connected in tandem, as the folding of PDZ1 strictly depends on the covalent attachment of PDZ2. The crystal structure of GRIP1 PDZ12 in complex with the Fras1 C-terminal peptide reveals that the PDZ12 tandem forms a supramodule in which only the peptide-binding groove of PDZ1 is bound with the Fras1 peptide. The GRIP1 PDZ12/Fras1 peptide complex not only provides a mechanistic explanation of the link between GRIP1 and the Fraser syndrome but may also serve as a foundation for searching for potential mutations in GRIP1 that could lead to the Fraser syndrome.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. The overall structure of the GRIP1 PDZ12 tandem in complex with the Fras1 peptide. (a) Ribbon diagram representation showing the stereoview of the backbone structure of the GRIP1 PDZ12 tandem in complex with the Fras1 peptide. PDZ1 (residues 48–135), PDZ2 (residues 145–240), and Loop[1–2] (residues 136–144) are colored blue, green, and yellow, respectively. (b) A semitransparent surface representation of the PDZ12 tandem showing that the two PDZ domains interact with each other in a front-to-back fashion to form a structurally intact supramodule. The figure also illustrates that the hypothetical target-binding groove of PDZ2 (highlighted with a red oval) is occupied by residues from the βA-, αA-, and the αA/βD-loop regions of PDZ1 and, therefore, inaccessible to peptide ligands. (c) Overlay plot of the backbone structures of PDZ1 and PDZ2 showing the similarity of their overall conformation. The different conformation of the βB/βC-loop between the two PDZ domains is highlighted by a purple oval.
Figure 5.
Fig. 5. Multiple sequence alignment of the PDZ12 tandem of GRIP from different species. The protein sequences were from rat, human, zebrafish, and fruit fly. In this diagram, residues that are identical and similar are shown in red and yellow boxes, respectively. The secondary structural elements are indicated above the alignment and are colored blue (for PDZ1) and green (for PDZ2). The amino acid residues in PDZ1 that are directly involved in the Fras1 peptide binding are highlighted with triangles, and the residues labeled with asterisks are critical for the interdomain interaction between PDZ1 and PDZ2.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 375, 1457-1468) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20461427 K.Kaufmann, N.Shen, L.Mizoue, and J.Meiler (2011).
A physical model for PDZ-domain/peptide interactions.
  J Mol Model, 17, 315-324.  
20509869 H.J.Lee, and J.J.Zheng (2010).
PDZ domains and their binding partners: structure, specificity, and modification.
  Cell Commun Signal, 8, 8.  
19153575 W.Feng, and M.Zhang (2009).
Organization and dynamics of PDZ-domain-related supramodules in the postsynaptic density.
  Nat Rev Neurosci, 10, 87-99.  
18640982 W.Wen, W.Liu, J.Yan, and M.Zhang (2008).
Structure basis and unconventional lipid membrane binding properties of the PH-C1 tandem of rho kinases.
  J Biol Chem, 283, 26263-26273.  
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.