PDBsum entry 4zzc

Membrane protein, transport protein

PDB id: 4zzc

Contents

Protein chains

311 a.a.

Ligands

ACT ×10

PLC ×10

LMT ×6

_XE ×30

Metals

_CL ×5

_NA ×6

Waters ×7

References listed in PDB file

Key reference

• Title: Structural basis for xenon inhibition in a cationic pentameric ligand-Gated ion channel.
• Authors: L.Sauguet, Z.Fourati, T.Prangé, M.Delarue, N.Colloc'H.
• Ref.: Plos One, 2016, 11, e0149795. [DOI no: 10.1371/journal.pone.0149795]
• PubMed id: 26910105

Note: In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above have been manually determined.

Abstract

GLIC receptor is a bacterial pentameric ligand-gated ion channel whose action is inhibited by xenon. Xenon has been used in clinical practice as a potent gaseous anaesthetic for decades, but the molecular mechanism of interactions with its integral membrane receptor targets remains poorly understood. Here we characterize by X-ray crystallography the xenon-binding sites within both the open and "locally-closed" (inactive) conformations of GLIC. Major binding sites of xenon, which differ between the two conformations, were identified in three distinct regions that all belong to the trans-membrane domain of GLIC: 1) in an intra-subunit cavity, 2) at the interface between adjacent subunits, and 3) in the pore. The pore site is unique to the locally-closed form where the binding of xenon effectively seals the channel. A putative mechanism of the inhibition of GLIC by xenon is proposed, which might be extended to other pentameric cationic ligand-gated ion channels.