3KEI

Crystal Structure of the GluA4 Ligand-Binding domain L651V mutant in complex with glutamate

3KEI の概要

• エントリーDOI: 10.2210/pdb3kei/pdb
• 関連するPDBエントリー: 3KFM
• 分子名称: Glutamate receptor 4, GLUTAMIC ACID (3 entities in total)
• 機能のキーワード: glua4, ampa receptor, ligand-gated ion channel, ligand-binding domain, l651v, alternative splicing, cell junction, cell membrane, glycoprotein, ion transport, ionic channel, lipoprotein, membrane, palmitate, postsynaptic cell membrane, receptor, synapse, transmembrane, transport, transport protein
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 57740.59

構造登録者

Gill, A.,Madden, D.R. (登録日: 2009-10-26, 公開日: 2010-02-09, 最終更新日: 2024-11-20)

主引用文献

Birdsey-Benson, A.,Gill, A.,Henderson, L.P.,Madden, D.R.
Enhanced efficacy without further cleft closure: reevaluating twist as a source of agonist efficacy in AMPA receptors.
J.Neurosci., 30:1463-1470, 2010

PubMed Abstract: AMPA receptors (AMPARs) are tetrameric ligand-gated ion channels that couple the energy of glutamate binding to the opening of a transmembrane channel. Crystallographic and electrophysiological analysis of AMPARs has suggested a coupling between (1) cleft closure in the bilobate ligand-binding domain (LBD), (2) the resulting separation of transmembrane helix attachment points across subunit dimers, and (3) agonist efficacy. In general, more efficacious agonists induce greater degrees of cleft closure and transmembrane separation than partial agonists. Several apparent violations of the cleft-closure/efficacy paradigm have emerged, although in all cases, intradimer separation remains as the driving force for channel opening. Here, we examine the structural basis of partial agonism in GluA4 AMPARs. We find that the L651V substitution enhances the relative efficacy of kainate without increasing either LBD cleft closure or transmembrane separation. Instead, the conformational change relative to the wild-type:kainate complex involves a twisting motion with the efficacy contribution opposite from that expected based on previous analyses. As a result, channel opening may involve transmembrane rearrangements with a significant rotational component. Furthermore, a two-dimensional analysis of agonist-induced GluA2 LBD motions suggests that efficacy is not a linearly varying function of lobe 2 displacement vectors, but is rather determined by specific conformational requirements of the transmembrane domains.

PubMed: 20107073
DOI: 10.1523/JNEUROSCI.4558-09.2010

実験手法

X-RAY DIFFRACTION (1.9 Å)