6V03

ELIC-propylammonium complex in POPC-only nanodiscs

6V03 の概要

• エントリーDOI: 10.2210/pdb6v03/pdb
• EMDBエントリー: 20968
• 分子名称: Gamma-aminobutyric-acid receptor subunit beta-1, 3-AMINOPROPANE (2 entities in total)
• 機能のキーワード: pentameric ligand-gated ion channels, popc, propylamonium, nanodisc, cys-loop receptor, membrane protein
• 由来する生物種: Dickeya dadantii (strain 3937)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 183914.81

構造登録者

Grosman, C.,Kumar, P. (登録日: 2019-11-18, 公開日: 2020-01-15, 最終更新日: 2024-03-06)

主引用文献

Kumar, P.,Wang, Y.,Zhang, Z.,Zhao, Z.,Cymes, G.D.,Tajkhorshid, E.,Grosman, C.
Cryo-EM structures of a lipid-sensitive pentameric ligand-gated ion channel embedded in a phosphatidylcholine-only bilayer.
Proc.Natl.Acad.Sci.USA, 117:1788-1798, 2020

PubMed Abstract: The lipid dependence of the nicotinic acetylcholine receptor from the electric organ has long been recognized, and one of the most consistent experimental observations is that, when reconstituted in membranes formed by zwitterionic phospholipids alone, exposure to agonist fails to elicit ion-flux activity. More recently, it has been suggested that the bacterial homolog ELIC ( ligand-gated ion channel) has a similar lipid sensitivity. As a first step toward the elucidation of the structural basis of this phenomenon, we solved the structures of ELIC embedded in palmitoyl-oleoyl-phosphatidylcholine- (POPC-) only nanodiscs in both the unliganded (4.1-Å resolution) and agonist-bound (3.3 Å) states using single-particle cryoelectron microscopy. Comparison of the two structural models revealed that the largest differences occur at the level of loop C-at the agonist-binding sites-and the loops at the interface between the extracellular and transmembrane domains (ECD and TMD, respectively). On the other hand, the transmembrane pore is occluded in a remarkably similar manner in both structures. A straightforward interpretation of these findings is that POPC-only membranes frustrate the ECD-TMD coupling in such a way that the "conformational wave" of liganded-receptor gating takes place in the ECD and the interfacial M2-M3 linker but fails to penetrate the membrane and propagate into the TMD. Furthermore, analysis of the structural models and molecular simulations suggested that the higher affinity for agonists characteristic of the open- and desensitized-channel conformations results, at least in part, from the tighter confinement of the ligand to its binding site; this limits the ligand's fluctuations, and thus delays its escape into bulk solvent.

PubMed: 31911476
DOI: 10.1073/pnas.1906823117

実験手法

ELECTRON MICROSCOPY (3.3 Å)