title: Mechanism of voltage gating in potassium channels.
abstract: The mechanism of ion channel voltage gating-how channels open and close in response to voltage changes-has been debated since Hodgkin and Huxley's seminal discovery that the crux of nerve conduction is ion flow across cellular membranes. Using all-atom molecular dynamics simulations, we show how a voltage-gated potassium channel (KV) switches between activated and deactivated states. On deactivation, pore hydrophobic collapse rapidly halts ion flow. Subsequent voltage-sensing domain (VSD) relaxation, including inward, 15-angstrom S4-helix motion, completes the transition. On activation, outward S4 motion tightens the VSD-pore linker, perturbing linker-S6-helix packing. Fluctuations allow water, then potassium ions, to reenter the pore; linker-S6 repacking stabilizes the open pore. We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data.
authors.affiliation: D E Shaw Research, New York, NY 10036, USA. morten.jensen@DEShawResearch.com
authors.forename: Morten Ø
authors.initials: MØ
authors.lastname: Jensen
authors.forename: Vishwanath
authors.initials: V
authors.lastname: Jogini
authors.forename: David W
authors.initials: DW
authors.lastname: Borhani
authors.forename: Abba E
authors.initials: AE
authors.lastname: Leffler
authors.forename: Ron O
authors.initials: RO
authors.lastname: Dror
authors.forename: David E
authors.initials: DE
authors.lastname: Shaw
mesh_terms: D000818:Animals; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D051663:Kv1.2 Potassium Channel / Q000737:chemistry* / Q000378:metabolism*; D008564:Membrane Potentials; D008954:Models, Biological; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D051669:Shab Potassium Channels / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D051663:Kv1.2 Potassium Channel; D011993:Recombinant Fusion Proteins; D051669:Shab Potassium Channels