title: Coupling between the voltage-sensing and pore domains in a voltage-gated potassium channel.
abstract: Voltage-dependent potassium (Kv), sodium (Nav), and calcium channels open and close in response to changes in transmembrane (TM) potential, thus regulating cell excitability by controlling ion flow across the membrane. An outstanding question concerning voltage gating is how voltage-induced conformational changes of the channel voltage-sensing domains (VSDs) are coupled through the S4-S5 interfacial linking helices to the opening and closing of the pore domain (PD). To investigate the coupling between the VSDs and the PD, we generated a closed Kv channel configuration from Aeropyrum pernix (KvAP) using atomistic simulations with experiment-based restraints on the VSDs. Full closure of the channel required, in addition to the experimentally determined TM displacement, that the VSDs be displaced both inwardly and laterally around the PD. This twisting motion generates a tight hydrophobic interface between the S4-S5 linkers and the C-terminal ends of the pore domain S6 helices in agreement with available experimental evidence.
authors.affiliation: Department of Chemistry, University of California, Irvine, CA 92697-2025, USA.
authors.forename: Eric V
authors.initials: EV
authors.lastname: Schow
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Freites
authors.forename: Alex
authors.initials: A
authors.lastname: Nizkorodov
authors.forename: Stephen H
authors.initials: SH
authors.lastname: White
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Tobias
mesh_terms: D000595:Amino Acid Sequence; D015640:Ion Channel Gating; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008564:Membrane Potentials; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D008051:Lipid Bilayers; D024642:Potassium Channels, Voltage-Gated