title: Mapping the sequence of conformational changes underlying selectivity filter gating in the K(v)11.1 potassium channel.
abstract: The potassium channel selectivity filter both discriminates between K(+) and sodium ions and contributes to gating of ion flow. Static structures of conducting (open) and nonconducting (inactivated) conformations of this filter are known; however, the sequence of protein rearrangements that connect these two states is not. We show that closure of the selectivity filter gate in the human K(v)11.1 K(+) channel (also known as hERG, for ether-a-go-go-related gene), a key regulator of the rhythm of the heartbeat, is initiated by K(+) exit, followed in sequence by conformational rearrangements of the pore domain outer helix, extracellular turret region, voltage sensor domain, intracellular domains and pore domain inner helix. In contrast to the simple wave-like sequence of events proposed for opening of ligand-gated ion channels, a complex spatial and temporal sequence of widespread domain motions connect the open and inactivated states of the K(v)11.1 K(+) channel.
authors.affiliation: Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, New South Wales, Australia. j.vandenberg@victorchang.edu.au
authors.forename: David T
authors.initials: DT
authors.lastname: Wang
authors.forename: Adam P
authors.initials: AP
authors.lastname: Hill
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Mann
authors.forename: Peter S
authors.initials: PS
authors.lastname: Tan
authors.forename: Jamie I
authors.initials: JI
authors.lastname: Vandenberg
mesh_terms: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry* / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D007700:Kinetics; D011188:Potassium / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D011188:Potassium