Crystal structure of GRIP1 PDZ6-peptide complex reveals the structural basis for class II PDZ target recognition and PDZ domain-mediated multimerization. Export

@article{citeulike:3091064, abstract = {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.}, address = {Department of Life Science, Kwangju Institute of Science and Technology, Gwangju 500-712, South Korea.}, author = {Im, Y. J. and Park, S. H. and Rho, S. H. and Lee, J. H. and Kang, G. B. and Sheng, M. and Kim, E. and Eom, S. H.}, citeulike-article-id = {3091064}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M212263200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12493751}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12493751}, day = {7}, doi = {10.1074/jbc.M212263200}, issn = {0021-9258}, journal = {The Journal of biological chemistry}, keywords = {pdz\_dimer, pdz\_peptide}, month = {March}, number = {10}, pages = {8501--8507}, posted-at = {2008-08-06 16:52:38}, priority = {2}, title = {Crystal structure of GRIP1 PDZ6-peptide complex reveals the structural basis for class II PDZ target recognition and PDZ domain-mediated multimerization.}, url = {http://dx.doi.org/10.1074/jbc.M212263200}, volume = {278}, year = {2003} }

TY - JOUR ID - citeulike:3091064 L3 - citeulike-article-id:3091064 N2 - 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. IS - 10 JF - The Journal of biological chemistry SN - 0021-9258 AD - Department of Life Science, Kwangju Institute of Science and Technology, Gwangju 500-712, South Korea. EP - 8507 TI - Crystal structure of GRIP1 PDZ6-peptide complex reveals the structural basis for class II PDZ target recognition and PDZ domain-mediated multimerization. VL - 278 SP - 8501 KW - pdz_dimer KW - pdz_peptide AU - Im, YJ AU - Park, SH AU - Rho, SH AU - Lee, JH AU - Kang, GB AU - Sheng, M AU - Kim, E AU - Eom, SH PY - 2003/03/07/ UR - http://dx.doi.org/10.1074/jbc.M212263200 ER -