1P1N

GluR2 Ligand Binding Core (S1S2J) Mutant L650T in Complex with Kainate

1P1N の概要

• エントリーDOI: 10.2210/pdb1p1n/pdb
• 関連するPDBエントリー: 1P1O 1P1Q 1P1U 1P1W
• 分子名称: Glutamate receptor 2, 3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE (3 entities in total)
• 機能のキーワード: ionotropic glutamate receptor, 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: 1
• 化学式量合計: 29422.86

構造登録者

Armstrong, N.,Mayer, M.L.,Gouaux, E. (登録日: 2003-04-13, 公開日: 2003-06-10, 最終更新日: 2021-10-27)

主引用文献

Armstrong, N.,Mayer, M.,Gouaux, E.
Tuning activation of the AMPA-sensitive GluR2 ion channel by genetic adjustment of agonist-induced conformational changes.
Proc.Natl.Acad.Sci.USA, 100:5736-5741, 2003

PubMed Abstract: The (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole) propionic acid (AMPA) receptor discriminates between agonists in terms of binding and channel gating; AMPA is a high-affinity full agonist, whereas kainate is a low-affinity partial agonist. Although there is extensive literature on the functional characterization of partial agonist activity in ion channels, structure-based mechanisms are scarce. Here we investigate the role of Leu-650, a binding cleft residue conserved among AMPA receptors, in maintaining agonist specificity and regulating agonist binding and channel gating by using physiological, x-ray crystallographic, and biochemical techniques. Changing Leu-650 to Thr yields a receptor that responds more potently and efficaciously to kainate and less potently and efficaciously to AMPA relative to the WT receptor. Crystal structures of the Leu-650 to Thr mutant reveal an increase in domain closure in the kainate-bound state and a partially closed and a fully closed conformation in the AMPA-bound form. Our results indicate that agonists can induce a range of conformations in the GluR2 ligand-binding core and that domain closure is directly correlated to channel activation. The partially closed, AMPA-bound conformation of the L650T mutant likely captures the structure of an agonist-bound, inactive state of the receptor. Together with previously solved structures, we have determined a mechanism of agonist binding and subsequent conformational rearrangements.

PubMed: 12730367
DOI: 10.1073/pnas.1037393100

実験手法

X-RAY DIFFRACTION (1.6 Å)