A Prokaryotic Perspective on Pentameric Ligand-Gated Ion Channel Structure and Function

Abstract

The X-ray structures of two prokaryotic pentameric ligand-gated ion channels (pLGICs) have provided first structural insight into the family at high resolution. The structure of GLIC, a proton-activated channel from the cyanobacterium Gloebacter violaceous shows an open conformation of the pore. The channel conducts cations with similar properties as the nicotinic acetylcholine receptor and is inhibited by the same set of open channel blockers. The transmembrane pore is funnel-shaped with a wide hydrophobic entrance at the extracellular side that narrows to a hydrophilic intracellular opening. In this region conserved residues coordinate ions which have lost a large part of their hydration shell.The structure of ELIC, a pLGIC from the plant pathogen Erwinia chrysanthemi shows a non-conducting conformation of the channel that was obtained in the absence of ligands. In its structure the extracellular half of the pore is occluded by bulky hydrophobic residues that likely prevent ion conduction. ELIC is activated by a set of primary amines that include the neurotransmitter GABA. The protein forms cation selective channels with large single channel conductance that slowly desensitize in the presence of ligands.The strong structural similarity to their eukaryotic counterparts combined with their comparably simpler functional behavior make ELIC and GLIC important model systems for the pLGIC family that will ultimately allow a detailed comprehension of mechanistic properties that are still only poorly understood.