title: Structural basis underlying the dual gate properties of KcsA.
abstract: KcsA is a prokaryotic pH-dependent potassium (K) channel. Its activation, by a decrease in the intracellular pH, is coupled with its subsequent inactivation, but the underlying mechanisms remain elusive. Here, we have investigated the conformational changes and equilibrium of KcsA by using solution NMR spectroscopy. Controlling the temperature and pH of KcsA samples produced three distinct methyl-TROSY and NOESY spectra, corresponding to the resting, activated, and inactivated states. The pH-dependence of the signals from the extracellular side was affected by the mutation of H25 on the intracellular side, indicating the coupled conformational changes of the extracellular and intracellular gates. K(+) titration and NOE experiments revealed that the inactivated state was obtained by the replacement of K(+) with H(2)O, which may interfere with the K(+)-permeation. This structural basis of the activation-coupled inactivation is closely related to the C-type inactivation of other K channels.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Imai
authors.forename: Masanori
authors.initials: M
authors.lastname: Osawa
authors.forename: Koh
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Ichio
authors.initials: I
authors.lastname: Shimada
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D011188:Potassium / Q000737:chemistry / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D048170:Streptomyces lividans / Q000737:chemistry* / Q000378:metabolism; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015221:Potassium Channels; C107790:prokaryotic potassium channel; D014867:Water; D011188:Potassium