title: Structural basis for allosteric coupling at the membrane-protein interface in Gloeobacter violaceus ligand-gated ion channel (GLIC).
abstract: Ligand binding at the extracellular domain of pentameric ligand-gated ion channels initiates a relay of conformational changes that culminates at the gate within the transmembrane domain. The interface between the two domains is a key structural entity that governs gating. Molecular events in signal transduction at the interface are poorly defined because of its intrinsically dynamic nature combined with functional modulation by membrane lipid and water vestibules. Here we used electron paramagnetic resonance spectroscopy to delineate protein motions underlying Gloeobacter violaceus ligand-gated ion channel gating in a membrane environment and report the interface conformation in the closed and the desensitized states. Extensive intrasubunit interactions were observed in the closed state that are weakened upon desensitization and replaced by newer intersubunit contacts. Gating involves major rearrangements of the interfacial loops, accompanied by reorganization of the protein-lipid-water interface. These structural changes may serve as targets for modulation of gating by lipids, alcohols, and amphipathic drug molecules.
authors: From the Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970.
authors: Phanindra
authors: P
authors: Velisetty
authors: Sreevatsa V
authors: SV
authors: Chalamalasetti
authors: Sudha
authors: S
authors: Chakrapani
mesh_terms: D000438:Alcohols / Q000378:metabolism; D000494:Allosteric Regulation; D000458:Cyanobacteria / Q000737:chemistry* / Q000378:metabolism; D015640:Ion Channel Gating / Q000502:physiology*; D058446:Ligand-Gated Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008563:Membrane Lipids / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
chemical_list: D000438:Alcohols; D058446:Ligand-Gated Ion Channels; D008024:Ligands; D008563:Membrane Lipids; D008565:Membrane Proteins
keywords: Cys-loop Receptors; Gating; Ion Channels; Membrane Reconstitution; Spectroscopy