title: Conformational Changes Underlying Desensitization of the Pentameric Ligand-Gated Ion Channel ELIC.
abstract: Structural rearrangements underlying functional transitions of pentameric ligand-gated ion channels (pLGICs) are not fully understood. Using (19)F nuclear magnetic resonance and electron spin resonance spectroscopy, we found that ELIC, a pLGIC from Erwinia chrysanthemi, expanded the extracellular end and contracted the intracellular end of its pore during transition from the resting to an apparent desensitized state. Importantly, the contraction at the intracellular end of the pore likely forms a gate to restrict ion transport in the desensitized state. This gate differs from the hydrophobic gate present in the resting state. Conformational changes of the TM2-TM3 loop were limited to the N-terminal end. The TM4 helices and the TM3-TM4 loop appeared relatively insensitive to agonist-mediated structural rearrangement. These results indicate that conformational changes accompanying functional transitions are not uniform among different ELIC regions. This work also revealed the co-existence of multiple conformations for a given state and suggested asymmetric conformational arrangements in a homomeric pLGIC.
authors.affiliation: Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: Monica N
authors.initials: MN
authors.lastname: Kinde
authors.affiliation: Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Lawless
authors.affiliation: Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA; Department of Computational & Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Mowrey
authors.affiliation: Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Saxena
authors.affiliation: Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA; Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA; Department of Structural Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA; Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA; Department of Computational & Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA. Electronic address: tangp@anes.upmc.edu.
authors.forename: Pei
authors.initials: P
authors.lastname: Tang
mesh_terms: D016974:Dickeya chrysanthemi / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D058446:Ligand-Gated Ion Channels / Q000737:chemistry*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation
chemical_list: D058446:Ligand-Gated Ion Channels