PDBsum entry 2qt5

Peptide binding protein

PDB id: 2qt5

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. Engineered: yes

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

Protein chains

P97879  (GRIP1_RAT) -  Glutamate receptor-interacting protein 1 from Rattus norvegicus

Seq: 1112 a.a.

Struc: 194 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

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.