1LBB

Crystal structure of the GluR2 ligand binding domain mutant (S1S2J-N754D) in complex with kainate at 2.1 A resolution

1LBB の概要

• エントリーDOI: 10.2210/pdb1lbb/pdb
• 関連するPDBエントリー: 1GR2 1LB8 1LB9 1LBC
• 分子名称: Glutamine receptor 2, 3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE (3 entities in total)
• 機能のキーワード: ampa receptor, glur2, s1s2, ligand-binding core, point mutation, n754d, agonist, kainate, 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: 29435.90

構造登録者

Sun, Y.,Olson, R.,Horning, M.,Armstrong, N.,Mayer, M.,Gouaux, E. (登録日: 2002-04-02, 公開日: 2002-06-05, 最終更新日: 2024-10-09)

主引用文献

Sun, Y.,Olson, R.,Horning, M.,Armstrong, N.,Mayer, M.,Gouaux, E.
Mechanism of glutamate receptor desensitization.
Nature, 417:245-253, 2002

PubMed Abstract: Ligand-gated ion channels transduce chemical signals into electrical impulses by opening a transmembrane pore in response to binding one or more neurotransmitter molecules. After activation, many ligand-gated ion channels enter a desensitized state in which the neurotransmitter remains bound but the ion channel is closed. Although receptor desensitization is crucial to the functioning of many ligand-gated ion channels in vivo, the molecular basis of this important process has until now defied analysis. Using the GluR2 AMPA-sensitive glutamate receptor, we show here that the ligand-binding cores form dimers and that stabilization of the intradimer interface by either mutations or allosteric modulators reduces desensitization. Perturbations that destabilize the interface enhance desensitization. Receptor activation involves conformational changes within each subunit that result in an increase in the separation of portions of the receptor that are linked to the ion channel. Our analysis defines the dimer interface in the resting and activated state, indicates how ligand binding is coupled to gating, and suggests modes of dimer dimer interaction in the assembled tetramer. Desensitization occurs through rearrangement of the dimer interface, which disengages the agonist-induced conformational change in the ligand-binding core from the ion channel gate.

PubMed: 12015593
DOI: 10.1038/417245a

実験手法

X-RAY DIFFRACTION (2.1 Å)