3D structure and allosteric modulation of the transmembrane domain of pentameric ligand-gated ion channels.
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.
Baenziger
John E
JE
Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Rd, Ottawa, ON, Canada. John.Baenziger@uottawa.ca
Corringer
Pierre-Jean
PJ
D000494:Allosteric Regulation / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology; D058446:Ligand-Gated Ion Channels / Q000502:physiology*; D011487:Protein Conformation; D011963:Receptors, GABA-A / Q000378:metabolism; D018009:Receptors, Glycine / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism
D058446:Ligand-Gated Ion Channels; D011963:Receptors, GABA-A; D018009:Receptors, Glycine; D011978:Receptors, Nicotinic