PDBsum entry 1p1e

Protein binding

PDB id: 1p1e

Contents

Protein chain

101 a.a. *

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Tandem pdz repeats in glutamate receptor-Interacting proteins have a novel mode of pdz domain-Mediated target binding.

Authors

W.Feng, Y.Shi, M.Li, M.Zhang.

Ref.

Nat Struct Biol, 2003, 10, 972-978. [DOI no: 10.1038/nsb992]

PubMed id

14555997

Abstract

The interaction of the glutamate receptor subunits 2 and 3 (GluR2/3) with multi-PDZ domain glutamate receptor-interacting protein (GRIP) is important for the synaptic trafficking and clustering of the receptors. Binding of GluR2/3 to GRIP requires both the fourth and fifth PDZ domains (PDZ4 and PDZ5) to be covalently linked, although only one PDZ domain is directly involved in binding to the receptor tail. To elucidate the molecular basis of this mode of PDZ domain-mediated target recognition, we solved the solution structures of the PDZ45 tandem and the isolated PDZ4 of GRIP. The two PDZ domains form a compact structure with a fixed interdomain orientation. The interdomain packing and the stable folding of both PDZ domains require a short stretch of amino acids N-terminal to PDZ4 and a conserved linker connecting PDZ4 and PDZ5. PDZ4 contains a deformed aB-bB groove that is unlikely to bind to carboxyl peptides. Instead, the domain stabilizes the structure of PDZ5.

Figure 1.
Figure 1. Structure of PDZ45 tandem repeats of GRIP1. (a) Stereo view showing the backbone (N, C and C') of 20 superimposed NMR-derived structure of PDZ45 (residues 463 -658). The structures are superimposed against the averaged structure using residues 463 -658. Residues 463 -558 containing PDZ4 and the N-terminal extension are violet, residues 559 -568 encompassing the central linker are red and residues 569 -658 containing PDZ5 are blue. (b) Ribbon diagram of a representative NMR structure of PDZ45, colored as in panel a. The secondary structures of each PDZ domain are labeled following the standard scheme initially adopted by Doyle et al5. A prime following each secondary structure element (e.g., A') in PDZ5 is used to indicate the same secondary structure as in PDZ4. The -strand in the central linker is denoted as L. The two PDZ domains are related by a 32 Å translation and a 90° rotation around an axis roughly colinear with the direction of translation. (c) Molecular surface representation of PDZ45 showing the tight packing of the two domains into a supramodular structure. The surface is drawn according to its electric potential (red, negative; blue, positive). The molecule is drawn in the same orientation as in b.

Figure 3.
Figure 3. Solution structure of PDZ4. (a) Stereo view showing the backbone (N, C and C') of 20 superimposed NMR-derived structures of PDZ4 (residues 463 -567). The structures are superimposed against the averaged structure using residues 468 -530 and 536 -558. Both the N-terminal extension and the central linker of PDZ45 are ill defined. (b) Ribbon diagram of a representative of PDZ4 with the potential peptide-binding channel ( B - B groove) facing outwards.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2003, 10, 972-978) copyright 2003.