1n7f

From Proteopedia

Revision as of 14:27, 15 February 2008

Crystal structure of the sixth PDZ domain of GRIP1 in complex with liprin C-terminal peptide

Overview

PDZ domains bind to short segments within target proteins in a, sequence-specific fashion. Glutamate receptor-interacting protein, (GRIP)/ABP family proteins contain six to seven PDZ domains and interact, via the sixth PDZ domain (class II) with the C termini of various proteins, including liprin-alpha. In addition the PDZ456 domain mediates the, formation of homo- and heteromultimers of GRIP proteins. To better, understand the structural basis of peptide recognition by a class II PDZ, domain and PDZ-mediated multimerization, we determined the crystal, structures of the GRIP1 PDZ6 domain alone and in complex with a synthetic, C-terminal octapeptide of human liprin-alpha at resolutions of 1.5 and 1.8, A, respectively. Remarkably, unlike other class II PDZ domains, Ile-736 at, alphaB5 rather than conserved Leu-732 at alphaB1 makes a direct, hydrophobic contact with the side chain of the Tyr at the -2 position of, the ligand. Moreover, the peptide-bound structure of PDZ6 shows a slight, reorientation of helix alphaB, indicating that the second hydrophobic, pocket undergoes a conformational adaptation to accommodate the bulkiness, of the Tyr side chain, and forms an antiparallel dimer through an, interface located at a site distal to the peptide-binding groove. This, configuration may enable formation of GRIP multimers and efficient, clustering of GRIP-binding proteins.

About this Structure

1N7F is a Protein complex structure of sequences from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Crystal structure of GRIP1 PDZ6-peptide complex reveals the structural basis for class II PDZ target recognition and PDZ domain-mediated multimerization., Im YJ, Park SH, Rho SH, Lee JH, Kang GB, Sheng M, Kim E, Eom SH, J Biol Chem. 2003 Mar 7;278(10):8501-7. Epub 2002 Dec 18. PMID:12493751

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