title: Energetic role of the paddle motif in voltage gating of Shaker K(+) channels.
abstract: Voltage-gated ion channels underlie rapid electric signaling in excitable cells. Electrophysiological studies have established that the N-terminal half of the fourth transmembrane segment ((NT)S4) of these channels is the primary voltage sensor, whereas crystallographic studies have shown that (NT)S4 is not located within a proteinaceous pore. Rather, (NT)S4 and the C-terminal half of S3 ((CT)S3 or S3b) form a helix-turn-helix motif, termed the voltage-sensor paddle. This unexpected structural finding raises two fundamental questions: does the paddle motif also exist in voltage-gated channels in a biological membrane, and, if so, what is its function in voltage gating? Here, we provide evidence that the paddle motif exists in the open state of Drosophila Shaker voltage-gated K(+) channels expressed in Xenopus oocytes and that (CT)S3 acts as an extracellular hydrophobic 'stabilizer' for (NT)S4, thus biasing the gating chemical equilibrium toward the open state.
authors.affiliation: Department of Physiology, Howard Hughes Medical Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Xu
authors.forename: Yajamana
authors.initials: Y
authors.lastname: Ramu
authors.forename: Hyeon-Gyu
authors.initials: HG
authors.lastname: Shin
authors.forename: Jayden
authors.initials: J
authors.lastname: Yamakaze
authors.forename: Zhe
authors.initials: Z
authors.lastname: Lu
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D015870:Gene Expression; D009865:Oocytes / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry* / Q000378:metabolism*; D014981:Xenopus
chemical_list: D029721:Drosophila Proteins; D011994:Recombinant Proteins; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels
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