3D structure and allosteric modulation of the transmembrane domain of pentameric ligand-gated ion channels.

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Baenziger JE, Corringer PJ

3D structure and allosteric modulation of the transmembrane domain of pentameric ligand-gated ion channels.

Neuropharmacology. 2011 Jan;60(1):116-25. doi: 10.1016/j.neuropharm.2010.08.007. Epub 2010 Aug 14.

PubMed ID

20713066 [ View in PubMed

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Abstract

Pentameric ligand-gated ion channels mediate rapid chemo-electric signal transduction in animals. The active site of this family of proteins is their ion channel pore, which is located at the center of the transmembrane domain. The opening/closing motions of the channel pore are governed by the binding of neurotransmitter to the extracellular domain, but also by allosteric effectors acting within the transmembrane domain. Here, we review the structure of the transmembrane domain as well as its role in the allosteric modulation of pentameric ligand-gated ion channel function. We focus on two examples: the interactions of nicotinic ACh receptors with lipids, for which a novel "uncoupled" state has been proposed, and the interactions of GABA(A) and Glycine receptors with allosteric modulators, such as general anesthetics, ethanol and neurosteroids. We revisit these data in light of the recently solved X-ray structures of bacterial members of the family, which provide atomic-resolution insight into the structures of both the transmembrane domain and associated lipids.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ethanol	Glycine receptor subunit alpha-1	Protein	Humans	Yes	Agonist	Details
Ethanol	Glycine receptor subunit alpha-2	Protein	Humans	Yes	Agonist	Details