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PDZ1 Domain Of Synapse Associated Protein 97
Structural highlights
FunctionDLG1_RAT Essential multidomain scaffolding protein required for normal development (By similarity). Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. Regulates the excitability of cardiac myocytes by modulating the functional expression of Kv4 channels. Functional regulator of Kv1.5 channel (By similarity). May play a role in adherens junction assembly, signal transduction, cell proliferation, synaptogenesis and lymphocyte activation.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe synapse-associated protein-97 (SAP97) is important in the proper trafficking and cell surface maintenance of the N-methyl-D-aspartate ionotropic glutamate receptor. The molecular scaffold/receptor interaction is mediated by the association of the C terminus of the NR2B subunit of the N-methyl-D-aspartate receptor with the PDZ domains of SAP97. Here, we characterize the binding of the C terminus of NR2B with the PDZ domains of SAP97 and determine the structure of the PDZ1-NR2B complex employing high-resolution NMR. Based on fluorescence anisotropy, the NR2B subunit binds to the first and second PDZ domains of SAP97, with higher affinity for PDZ2; no appreciable binding to PDZ3 could be measured. The structural features of the NR2B bound to PDZ1 is consistent with the canonical PDZ-binding motif with the glutamic acid at the -3 position of the C terminus (i.e. -E-S-D-V) interacting with the beta2/beta3 loop. Two sites within the loop of PDZ1 were replaced with the corresponding residue from PDZ2, D243G and P245Q. The former mutation, designed to remove a possible Coulombic repulsion between E(-3)(NR2B) and Asp-243 (PDZ1) has only a minimal effect on binding. The P245Q mutation leads to a 2-fold increase in binding affinity of NR2B, approaching that observed for wild-type PDZ2. These results indicate that modification of the beta2/beta3 loop provides an avenue for regulating the ligand specificity of PDZ domains. Structural characterization of the intermolecular interactions of synapse-associated protein-97 with the NR2B subunit of N-methyl-D-aspartate receptors.,Wang L, Piserchio A, Mierke DF J Biol Chem. 2005 Jul 22;280(29):26992-6. Epub 2005 Jun 1. PMID:15929985[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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