Role of conserved glycines in pH gating of Kir1.1 (ROMK)

Biophysical Journal
H SackinHui Li

Abstract

Gating of inward rectifier Kir1.1 potassium channels by internal pH is believed to occur when large hydrophobic leucines, on each of the four subunits, obstruct the permeation path at the cytoplasmic end of the inner transmembrane helices (TM2). In this study, we examined whether closure of the channel at this point involves bending of the inner helix at one or both of two highly conserved glycine residues (corresponding to G134 and G143 in KirBac1.1) that have been proposed as putative "gating hinges" for potassium channels. Replacement of these conserved inner helical glycines by less flexible alanines did not abolish gating but shifted the apparent pKa from 6.6 +/- 0.01 (wild-type) to 7.1 +/- 0.01 for G157A-Kir1.1b, and to 7.3 +/- 0.01 for G148A-Kir1.1b. When both glycines were mutated the effect was additive, shifting the pKa by 1.2 pH units to 7.8 +/- 0.04 for the double mutant: G157A+G148A. At this pKa, the double mutant would remain completely closed under physiological conditions. In contrast, when the glycine at G148 was replaced by a proline, the pKa was shifted in the opposite direction from 6.6 +/- 0.01 (wild-type) to 5.7 +/- 0.01 for G148P. Although conserved glycines at G148 and G157 made it significantly easier t...Continue Reading

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Citations

Dec 24, 2008·The Journal of Biological Chemistry·Andrew K StewartSeth L Alper
Nov 13, 2008·The Journal of General Physiology·Janice L RobertsonBenoît Roux
May 22, 2009·American Journal of Physiology. Renal Physiology·Paul A Welling, Kevin Ho
Oct 26, 2011·The Journal of Physiology·Johan M EdvinssonLawrence G Palmer
May 15, 2007·Biophysical Journal·Henry SackinD Eric Walters
Mar 1, 2011·Biophysical Journal·Henry SackinLei Yang
Apr 29, 2015·PloS One·Ivan Sazanavets, Jim Warwicker
Jun 11, 2008·Chembiochem : a European Journal of Chemical Biology·Yasuo NagaokaStephen J Tucker
Apr 4, 2008·American Journal of Physiology. Cell Physiology·Alain J LabroDirk J Snyders
Jan 21, 2010·Physiological Reviews·Hiroshi HibinoYoshihisa Kurachi
Jun 21, 2017·The Journal of Biological Chemistry·Brighid M O'DonnellJeffrey L Brodsky
Jun 29, 2018·Pflügers Archiv : European journal of physiology·S HeringE N Timin
Mar 21, 2015·Journal of Chemical Information and Modeling·Tobias LinderAnna Stary-Weinzinger

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