2F36

Crystal Structure of the GluR5 Ligand Binding Core Dimer with Glutamate At 2.1 Angstroms Resolution

2F36 の概要

• エントリーDOI: 10.2210/pdb2f36/pdb
• 関連するPDBエントリー: 1TXF 2F34 2F35
• 分子名称: GLUTAMATE RECEPTOR, IONOTROPIC KAINATE 1, SULFATE ION, GLUTAMIC ACID, ... (4 entities in total)
• 機能のキーワード: membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P22756
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 117818.89

構造登録者

Mayer, M.L. (登録日: 2005-11-18, 公開日: 2006-04-04, 最終更新日: 2024-11-06)

主引用文献

Mayer, M.L.,Ghosal, A.,Dolman, N.P.,Jane, D.E.
Crystal structures of the kainate receptor GluR5 ligand binding core dimer with novel GluR5-selective antagonists.
J.Neurosci., 26:2852-2861, 2006

PubMed Abstract: Glutamate receptor (GluR) ion channels mediate fast synaptic transmission in the mammalian CNS. Numerous crystallographic studies, the majority on the GluR2-subtype AMPA receptor, have revealed the structural basis for binding of subtype-specific agonists. In contrast, because there are far fewer antagonist-bound structures, the mechanisms for antagonist binding are much less well understood, particularly for kainate receptors that exist as multiple subtypes with a distinct biology encoded by the GluR5-7, KA1, and KA2 genes. We describe here high-resolution crystal structures for the GluR5 ligand-binding core complex with UBP302 and UBP310, novel GluR5-selective antagonists. The crystal structures reveal the structural basis for the high selectivity for GluR5 observed in radiolabel displacement assays for the isolated ligand binding cores of the GluR2, GluR5, and GluR6 subunits and during inhibition of glutamate-activated currents in studies on full-length ion channels. The antagonists bind via a novel mechanism and do not form direct contacts with the E723 side chain as occurs in all previously solved AMPA and kainate receptor agonist and antagonist complexes. This results from a hyperextension of the ligand binding core compared with previously solved structures. As a result, in dimer assemblies, there is a 22 A extension of the ion channel linkers in the transition from antagonist- to glutamate-bound forms. This large conformational change is substantially different from that described for AMPA receptors, was not possible to predict from previous work, and suggests that glutamate receptors are capable of much larger movements than previously thought.

PubMed: 16540562
DOI: 10.1523/JNEUROSCI.0123-06.2005

実験手法

X-RAY DIFFRACTION (2.11 Å)