3U92

Crystal structure of the GluK3 ligand binding domain complex with kainate and zinc: P2221 form

3U92 の概要

• エントリーDOI: 10.2210/pdb3u92/pdb
• 関連するPDBエントリー: 1S50 1TXF 3S9E 3U93 3U94
• 分子名称: Glutamate receptor, ionotropic kainate 3, 3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE, ZINC ION, ... (5 entities in total)
• 機能のキーワード: membrane protein, ion channel
• 由来する生物種: Rattus norvegicus (rat); 詳細
• 細胞内の位置: Cell membrane; Multi-pass membrane protein: P42264
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59127.38

構造登録者

Kumar, J.,Mayer, M.L. (登録日: 2011-10-17, 公開日: 2012-09-26, 最終更新日: 2024-10-30)

主引用文献

Veran, J.,Kumar, J.,Pinheiro, P.S.,Athane, A.,Mayer, M.L.,Perrais, D.,Mulle, C.
Zinc Potentiates GluK3 Glutamate Receptor Function by Stabilizing the Ligand Binding Domain Dimer Interface.
Neuron, 76:565-578, 2012

PubMed Abstract: Kainate receptors (KARs) play a key role in the regulation of synaptic networks. Here, we show that zinc, a cation released at a subset of glutamatergic synapses, potentiates glutamate currents mediated by homomeric and heteromeric KARs containing GluK3 at 10-100 μM concentrations, whereas it inhibits other KAR subtypes. Potentiation of GluK3 currents is mainly due to reduced desensitization, as shown by kinetic analysis and desensitization mutants. Crystallographic and mutation analyses revealed that a specific zinc binding site is formed at the base of the ligand binding domain (LBD) dimer interface by a GluK3-specific aspartate (Asp759), together with two conserved residues, His762 and Asp730, the latter located on the partner subunit. In addition, we propose that tetrameric GluK2/GluK3 receptors are likely assembled as pairs of heterodimeric LBDs. Therefore, zinc binding stabilizes the labile GluK3 dimer interface, slows desensitization, and potentiates currents, providing a mechanism for KAR potentiation at glutamatergic synapses.

PubMed: 23141068
DOI: 10.1016/j.neuron.2012.08.027

実験手法

X-RAY DIFFRACTION (1.9 Å)