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Please use this identifier to cite or link to this item: http://dspace.utalca.cl/handle/1950/4631

Title: Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel
Authors: Niemeyer, M.I.
Gonzalez-Nilo, F.
Zuniga, L.
Gonzalez, W.
Cid, L.P.
Sepulveda, F.V.
Keywords: KCNK channels; molecular simulation; TALK-2; TASK-2
Issue Date: 2007
Publisher: PNAS
Citation: Proceedings of the National Academy of Sciences of the United States of America 104 (2): 666-671
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 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 amino acids within a protein.
Description: Fernando D. González-Nilo and Wendy González. Centro de Bioinformática y Simulación Molecular, Universidad de Talca, 2 Norte 685, Talca 346-0000, Chile.
URI: http://dspace.utalca.cl/handle/1950/4631
ISSN: 0027-8424
Appears in Collections:Artículos en publicaciones ISI - Universidad de Talca

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