title: Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore opening.
abstract: In voltage-gated K(+) channels, membrane depolarization induces an upward movement of the voltage-sensing domains (VSD) that triggers pore opening. KCNQ1 is a voltage-gated K(+) channel and its gating behaviour is substantially modulated by auxiliary subunit KCNE proteins. KCNE1, for example, markedly shifts the voltage dependence of KCNQ1 towards the positive direction and slows down the activation kinetics. Here we identify two phenylalanine residues on KCNQ1, Phe232 on S4 (VSD) and Phe279 on S5 (pore domain) to be responsible for the gating modulation by KCNE1. Phe232 collides with Phe279 during the course of the VSD movement and hinders KCNQ1 channel from opening in the presence of KCNE1. This steric hindrance caused by the bulky amino-acid residues destabilizes the open state and thus shifts the voltage dependence of KCNQ1/KCNE1 channel.
authors.affiliation: 1] Division of Biophysics and Neurobiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan [2] Department of Physiological Sciences, Hayama, Kanagawa 240-0193, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakajo
authors.affiliation: 1] Division of Biophysics and Neurobiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan [2] Department of Physiological Sciences, Hayama, Kanagawa 240-0193, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kubo
mesh_terms: D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010649:Phenylalanine / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C489622:KCNE1 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated; D010649:Phenylalanine