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1zok
From Proteopedia
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PDZ1 Domain Of Synapse Associated Protein 97
Overview
The 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.
About this Structure
1ZOK is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 16:17:39 2008
