3S9E

Crystal structure of the kainate receptor GluK3 ligand binding domain in complex with (S)-glutamate

3S9E の概要

• エントリーDOI: 10.2210/pdb3s9e/pdb
• 関連するPDBエントリー: 4MH5
• 分子名称: Glutamate receptor, ionotropic kainate 3, GLUTAMIC ACID, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: agonist, ionotropic glutamate receptor, glutamate, membrane, membrane protein
• 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: 59066.95

構造登録者

Venskutonyte, R.,Frydenvang, K.,Gajhede, M.,Kastrup, J.S. (登録日: 2011-06-01, 公開日: 2011-09-28, 最終更新日: 2024-11-06)

主引用文献

Venskutonyte, R.,Frydenvang, K.,Gajhede, M.,Bunch, L.,Pickering, D.S.,Kastrup, J.S.
Binding site and interlobe interactions of the ionotropic glutamate receptor GluK3 ligand binding domain revealed by high resolution crystal structure in complex with (S)-glutamate.
J.Struct.Biol., 176:307-314, 2011

PubMed Abstract: Ionotropic glutamate receptors (iGluRs) are involved in excitatory signal transmission throughout the central nervous system and their malfunction is associated with various health disorders. GluK3 is a subunit of iGluRs, belonging to the subfamily of kainate receptors (GluK1-5). Several crystal structures of GluK1 and GluK2 ligand binding domains have been determined in complex with agonists and antagonists. However, little is known about the molecular mechanisms underlying GluK3 ligand binding properties and no compounds displaying reasonable selectivity towards GluK3 are available today. Here, we present the first X-ray crystal structure of the ligand binding domain of GluK3 in complex with glutamate, determined to 1.6Å resolution. The structure reveals a conserved glutamate binding mode, characteristic for iGluRs, and a water molecule network in the glutamate binding site similar to that seen in GluK1. In GluK3, a slightly lower degree of domain closure around glutamate is observed compared to most other kainate receptor structures with glutamate. The volume of the GluK3 glutamate binding cavity was found to be of intermediate size between those of GluK1 and GluK2. The residues in GluK3 contributing to the subfamily differences in the binding sites are primarily: Thr520, Ala691, Asn722, Leu736 and Thr742. The GluK3 ligand binding domain seems to be less stabilized through interlobe interactions than GluK1 and this may contribute to the faster desensitization kinetics of GluK3.

PubMed: 21907808
DOI: 10.1016/j.jsb.2011.08.014

実験手法

X-RAY DIFFRACTION (1.6 Å)