3RQU

Crystal structure of a prokaryotic pentameric ligand-gated ion channel, ELIC

3RQU の概要

• エントリーDOI: 10.2210/pdb3rqu/pdb
• 関連するPDBエントリー: 3RQW
• 分子名称: ELIC Pentameric Ligand Gated Ion Channel from Erwinia Chrysanthemi, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: ion channel, membrane, transport protein
• 由来する生物種: Dickeya dadantii (Erwinia chrysanthemi)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 372090.63

構造登録者

Pan, J.J.,Chen, Q.,Yoshida, K.,Cohen, A.,Kong, X.P.,Xu, Y.,Tang, P. (登録日: 2011-04-28, 公開日: 2012-03-07, 最終更新日: 2023-09-13)

主引用文献

Pan, J.,Chen, Q.,Willenbring, D.,Yoshida, K.,Tillman, T.,Kashlan, O.B.,Cohen, A.,Kong, X.P.,Xu, Y.,Tang, P.
Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine.
Nat Commun, 3:714-714, 2012

PubMed Abstract: ELIC, the pentameric ligand-gated ion channel from Erwinia chrysanthemi, is a prototype for Cys-loop receptors. Here we show that acetylcholine is a competitive antagonist for ELIC. We determine the acetylcholine-ELIC cocrystal structure to a 2.9-Å resolution and find that acetylcholine binding to an aromatic cage at the subunit interface induces a significant contraction of loop C and other structural rearrangements in the extracellular domain. The side chain of the pore-lining residue F247 reorients and the pore size consequently enlarges, but the channel remains closed. We attribute the inability of acetylcholine to activate ELIC primarily to weak cation-π and electrostatic interactions in the pocket, because an acetylcholine derivative with a simple quaternary-to-tertiary ammonium substitution activates the channel. This study presents a compelling case for understanding the structural underpinning of the functional relationship between agonism and competitive antagonism in the Cys-loop receptors, providing a new framework for developing novel therapeutic drugs.

PubMed: 22395605
DOI: 10.1038/ncomms1703

実験手法

X-RAY DIFFRACTION (3.089 Å)