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Please use this identifier to cite or link to this item: http://dspace.utalca.cl/handle/1950/8919

Title: Gating of a pH-Sensitive K-2P Potassium Channel by an Electrostatic Effect of Basic Sensor Residues on the Selectivity Filter
Authors: Zuniga, L.
Marquez, V.
Gonzalez-Nilo, F.D.
Chipot, C.
Cid, L.P.
Sepulveda, F.V.
Niemeyer, M.I.
Issue Date: Jan-2011
Citation: PLOS ONE Volume: 6 Issue: 1 Article Number: e16141 DOI: 10.1371/journal.pone.0016141
Abstract: K+ channels share common selectivity characteristics but exhibit a wide diversity in how they are gated open. Leak K-2P K+ channels TASK-2, TALK-1 and TALK-2 are gated open by extracellular alkalinization. The mechanism for this alkalinization-dependent gating has been proposed to be the neutralization of the side chain of a single arginine (lysine in TALK-2) residue near the pore of TASK-2, which occurs with the unusual pK(a) of 8.0. We now corroborate this hypothesis by transplanting the TASK-2 extracellular pH (pH(o)) sensor in the background of a pH(o)-insensitive TASK-3 channel, which leads to the restitution of pH(o)-gating. Using a concatenated channel approach, we also demonstrate that for TASK-2 to open, pH(o) sensors must be neutralized in each of the two subunits forming these dimeric channels with no apparent cross-talk between the sensors. These results are consistent with adaptive biasing force analysis of K+ permeation using a model selectivity filter in wild-type and mutated channels. The underlying free-energy profiles confirm that either a doubly or a singly charged pH(o) sensor is sufficient to abolish ion flow. Atomic detail of the associated mechanism reveals that, rather than a collapse of the pore, as proposed for other K-2P channels gated at the selectivity filter, an increased height of the energetic barriers for ion translocation accounts for channel blockade at acid pHo. Our data, therefore, strongly suggest that a cycle of protonation/deprotonation of pH(o)-sensing arginine 224 side chain gates the TASK-2 channel by electrostatically tuning the conformational stability of its selectivity filter.
Description: Marquez, V (Marquez, Valeria); Gonzalez-Nilo, FD (Gonzalez-Nilo, Fernando D.). Univ Talca, Ctr Bioinformat & Simulac Mol, Talca, Chile
URI: http://dspace.utalca.cl/handle/1950/8919
ISSN: 1932-6203
Appears in Collections:Artículos en publicaciones ISI - Universidad de Talca

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