1ZOK

PDZ1 Domain Of Synapse Associated Protein 97

1ZOK の概要

• エントリーDOI: 10.2210/pdb1zok/pdb
• 分子名称: Presynaptic protein SAP97 (1 entity in total)
• 機能のキーワード: pdz, pdz1, sap97, synapse associated protein 97, beta strand, helix, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• 細胞内の位置: Membrane; Peripheral membrane protein (By similarity): Q62696
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10089.32

構造登録者

Wang, L.,Piserchio, A.,Mierke, D.F. (登録日: 2005-05-13, 公開日: 2005-06-07, 最終更新日: 2024-05-22)

主引用文献

Wang, L.,Piserchio, A.,Mierke, D.F.
Structural Characterization of the Intermolecular Interactions of Synapse-associated Protein-97 with the NR2B Subunit of N-Methyl-D-aspartate Receptors.
J.Biol.Chem., 280:26992-26996, 2005

PubMed Abstract: 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.

PubMed: 15929985
DOI: 10.1074/jbc.M503555200

実験手法

SOLUTION NMR