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Please use this identifier to cite or link to this item: http://dspace.utalca.cl/handle/1950/4657

Title: Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel.
Authors: Gonzalez-Nilo, F.
Niemeyer, M.I.
Zuniga, L.
Gonzalez, W.
Cid, P.L.
Sepulveda, F.V.
Issue Date: 2007
Publisher: Biophysical Society
Citation: Biophysical Journal: 256A-256A
Abstract: Potassium channels share a common selectivity filter that determines the conduction characteristics of the pore. Diversity in K+ channels is given by how they are gated open. TASK-2, TALK-1 and TALK-2 are two-pore region (2P) KCNK K+ channels gated open by extracellular alkalinization. We have explored the mechanism for this alkalinization-dependent gating using molecular simulation and site-directed mutagenesis followed by functional assay. We show that the side-chain of a single arginine residue (R224) near the pore senses pH in TASK-2 with an unusual pKa of 8.0, a shift likely due to its hydrophobic environment. R224 would block the channel through an electrostatic effect on the pore, a situation relieved by its deprotonation by alkalinization. A lysine residue in TALK-2 fulfills the same role, but with a largely unchanged pKa, which correlates with an environment that stabilizes its positive charge. In addition to suggesting a unified alkaline pH-gating mechanisms within the TALK subfamily of channels, our results illustrate in a physiological context the principle that hydrophobic environment can drastically modulate the pKa of charged aminoacids within a protein. Supported by FONDECYT grants 103-0838 (MIN) and 104-0254 (FG).
Description: Gonzalez Nilo, Danilo and Gonzalez, Wendy. Centro de Bioinformatica y Simulacion Molecular, Universidad de Talca, Talca, Chile.
URI: http://dspace.utalca.cl/handle/1950/4657
ISSN: 0006-3495
Appears in Collections:Artículos en publicaciones ISI - Universidad de Talca

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