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|Title: ||Neutralization of a single arginine residue gates open a two-pore domain, alkali-activated K+ channel.|
|Authors: ||González-Nilo, F.|
|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.|
|Appears in Collections:||Artículos en publicaciones ISI - Universidad de Talca|
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