title: Molecular mechanism of voltage sensor movements in a potassium channel.
abstract: Voltage-gated potassium channels are six-transmembrane (S1-S6) proteins that form a central pore domain (4 x S5-S6) surrounded by four voltage sensor domains (S1-S4), which detect changes in membrane voltage and control pore opening. Upon depolarization, the S4 segments move outward carrying charged residues across the membrane field, thereby leading to the opening of the pore. The mechanism of S4 motion is controversial. We have investigated how S4 moves relative to the pore domain in the prototypical Shaker potassium channel. We introduced pairs of cysteines, one in S4 and the other in S5, and examined proximity changes between each pair of cysteines during activation, using Cd2+ and copper-phenanthroline, which crosslink the cysteines with metal and disulphide bridges, respectively. Modelling of the results suggests a novel mechanism: in the resting state, the top of the S3b-S4 voltage sensor paddle lies close to the top of S5 of the adjacent subunit, but moves towards the top of S5 of its own subunit during depolarization--this motion is accompanied by a reorientation of S4 charges to the extracellular phase.
authors.affiliation: School of Biomedical Sciences, Leeds University, Leeds, UK.
authors.forename: David J S
authors.initials: DJ
authors.lastname: Elliott
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Neale
authors.forename: Qadeer
authors.initials: Q
authors.lastname: Aziz
authors.forename: James P
authors.initials: JP
authors.lastname: Dunham
authors.forename: Tim S
authors.initials: TS
authors.lastname: Munsey
authors.forename: Malcolm
authors.initials: M
authors.lastname: Hunter
authors.forename: Asipu
authors.initials: A
authors.lastname: Sivaprasadarao
mesh_terms: D000818:Animals; D002104:Cadmium / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D010618:Phenanthrolines / Q000737:chemistry / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051637:Shaker Superfamily of Potassium Channels; D014982:Xenopus laevis
chemical_list: D004220:Disulfides; D010618:Phenanthrolines; D015221:Potassium Channels; D021122:Protein Subunits; D051637:Shaker Superfamily of Potassium Channels; D002104:Cadmium; D003545:Cysteine