title: Structural sensitivity of a prokaryotic pentameric ligand-gated ion channel to its membrane environment.
abstract: Although the activity of the nicotinic acetylcholine receptor (nAChR) is exquisitely sensitive to its membrane environment, the underlying mechanisms remain poorly defined. The homologous prokaryotic pentameric ligand-gated ion channel, Gloebacter ligand-gated ion channel (GLIC), represents an excellent model for probing the molecular basis of nAChR sensitivity because of its high structural homology, relative ease of expression, and amenability to crystallographic analysis. We show here that membrane-reconstituted GLIC exhibits structural and biophysical properties similar to those of the membrane-reconstituted nAChR, although GLIC is substantially more thermally stable. GLIC, however, does not possess the same exquisite lipid sensitivity. In particular, GLIC does not exhibit the same propensity to adopt an uncoupled conformation where agonist binding is uncoupled from channel gating. Structural comparisons provide insight into the chemical features that may predispose the nAChR to the formation of an uncoupled state.
authors: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
authors: Jonathan M
authors: JM
authors: Labriola
authors: Akash
authors: A
authors: Pandhare
authors: Michaela
authors: M
authors: Jansen
authors: Michael P
authors: MP
authors: Blanton
authors: Pierre-Jean
authors: PJ
authors: Corringer
authors: John E
authors: JE
authors: Baenziger
mesh_terms: D001419:Bacteria / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D040681:Structural Homology, Protein
chemical_list: D001426:Bacterial Proteins; D007473:Ion Channels