1MM6

crystal structure of the GluR2 ligand binding core (S1S2J) in complex with quisqualate in a non zinc crystal form at 2.15 angstroms resolution

1MM6 の概要

• エントリーDOI: 10.2210/pdb1mm6/pdb
• 関連するPDBエントリー: 1FTJ 1FTM 1mm7 1MQG 1MQH 1MQI 1MQJ
• 分子名称: GLUTAMATE RECEPTOR 2, SULFATE ION, (S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC ACID, ... (5 entities in total)
• 機能のキーワード: ionotropic glutamate receptor, glur2, ligand binding core, s1s2, full agonist, quisqualate, complex, 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: P19491
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59293.99

構造登録者

Jin, R.,Horning, M.,Mayer, M.L.,Gouaux, E. (登録日: 2002-09-03, 公開日: 2003-02-04, 最終更新日: 2024-10-30)

主引用文献

Jin, R.,Horning, M.,Mayer, M.L.,Gouaux, E.
Mechanism of activation and selectivity in a ligand-gated ion channel: Structural and functional studies of GluR2 and quisqualate
Biochemistry, 41:15635-15643, 2002

PubMed Abstract: Glutamate is the major excitatory neurotransmitter in the mammalian brain. The (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole)propionic acid (AMPA)-subtype glutamate receptor, a ligand-gated ion channel, mediates most of the fast excitatory synaptic transmission in the mammalian central nervous system. Here we present electrophysiological, biochemical, and crystallographic data on the interactions between quisqualate and the GluR2 receptor ion channel and its corresponding ligand binding core. Quisqualate is a high-affinity, full agonist which like AMPA and glutamate elicits maximum peak current responses, and stabilizes the ligand binding core in a fully closed conformation, reinforcing the concept that full agonists produce similar conformational changes [Armstrong, N., and Gouaux, E. (2000) Neuron 28, 165-181]. Nevertheless, the mechanism of quisqualate binding is different from that of AMPA but similar to that of glutamate, illustrating that quisqualate is a faithful glutamate analogue. A detailed comparison of the three agonist complexes reveals distinct binding mechanisms, particularly in the region of a hydrophobic pocket that is proximal to the anionic gamma-substituents, and demonstrates the importance of agonist-water-receptor interactions. The hydrophobic pocket, which is predicted to vary in chemical character between receptor subtypes, probably plays an important role in determining receptor subtype specificity.

PubMed: 12501192
DOI: 10.1021/bi020583k

実験手法

X-RAY DIFFRACTION (2.15 Å)