title: Structural rearrangements underlying ligand-gating in Kir channels.
abstract: Inward rectifier potassium (Kir) channels are physiologically regulated by a wide range of ligands that all act on a common gate, although structural details of gating are unclear. Here we show, using small molecule fluorescent probes attached to introduced cysteines, the molecular motions associated with gating of KirBac1.1 channels. The accessibility of the probes indicates a major barrier to fluorophore entry to the inner cavity. Changes in fluorescence resonance energy transfer between fluorophores, attached to KirBac1.1 tetramers, show that phosphatidylinositol-4,5-bisphosphate-induced closure involves tilting and rotational motions of secondary structural elements of the cytoplasmic domain that couple ligand binding to a narrowing of the cytoplasmic vestibule. The observed ligand-dependent conformational changes in KirBac1.1 provide a general model for ligand-induced Kir channel gating at the molecular level.
authors.affiliation: Department of Cell Biology and Physiology and Center for Investigation of Membrane Excitability Diseases, Washington University School of Medicine, 425 S. Euclid Ave., St. Louis, Missouri 63110, USA.
authors.forename: Shizhen
authors.initials: S
authors.lastname: Wang
authors.forename: Sun-Joo
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sarah
authors.initials: S
authors.lastname: Heyman
authors.forename: Decha
authors.initials: D
authors.lastname: Enkvetchakul
authors.forename: Colin G
authors.initials: CG
authors.lastname: Nichols
mesh_terms: D001671:Biochemistry / Q000379:methods; D003545:Cysteine / Q000737:chemistry; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D005456:Fluorescent Dyes / Q000737:chemistry; D007295:Inositol Phosphates / Q000737:chemistry; D015640:Ion Channel Gating / Q000502:physiology; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009038:Motion; D009154:Mutation; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; D007295:Inositol Phosphates; D008024:Ligands; D008055:Lipids; D008081:Liposomes; D024661:Potassium Channels, Inwardly Rectifying; C066454:inositol 4,5-bisphosphate; D003545:Cysteine; D011188:Potassium