1m5z

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PDB ID 1m5z

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The PDZ7 of Glutamate Receptor Interacting Protein Binds to its Target via a Novel Hydrophobic Surface Area


Overview

Glutamate receptor interacting protein 1 (GRIP1) is a scaffold protein composed of seven PDZ (Postsynaptic synaptic density-95/Discs large/Zona occludens-1) domains. The protein plays important roles in the synaptic targeting of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The interaction between GRIP1 PDZ7 and a Ras guanine nucleotide exchange factor, GRASP-1, regulates synaptic distribution of AMPA receptors. Here, we describe the three-dimensional structure of GRIP1 PDZ7 determined by NMR spectroscopy. GRIP1 PDZ7 contains a closed carboxyl group-binding pocket and a narrow alphaB/betaB-groove that is not likely to bind to classical PDZ ligands. Unexpectedly, GRIP1 PDZ7 contains a large solvent-exposed hydrophobic surface at a site distinct from the conventional ligand-binding alphaB/betaB-groove. NMR titration experiments show that GRIP1 PDZ7 binds to GRASP-1 via this hydrophobic surface. Our data uncover a novel PDZ domain-mediated protein interaction mode that may be responsible for multimerization of other PDZ domain-containing scaffold proteins.

About this Structure

1M5Z is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

PDZ7 of glutamate receptor interacting protein binds to its target via a novel hydrophobic surface area., Feng W, Fan JS, Jiang M, Shi YW, Zhang M, J Biol Chem. 2002 Oct 25;277(43):41140-6. Epub 2002 Aug 23. PMID:12196542

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