BK channel opening involves side-chain reorientation of multiple deep-pore residues

Proceedings of the National Academy of Sciences of the United States of America
Xixi ChenRichard W Aldrich

Abstract

Three deep-pore locations, L312, A313, and A316, were identified in a scanning mutagenesis study of the BK (Ca(2+)-activated, large-conductance K(+)) channel S6 pore, where single aspartate substitutions led to constitutively open mutant channels (L312D, A313D, and A316D). To understand the mechanisms of the constitutive openness of these mutant channels, we individually mutated these three sites into the other 18 amino acids. We found that charged or polar side-chain substitutions at each of the sites resulted in constitutively open mutant BK channels, with high open probability at negative voltages, as well as a loss of voltage and Ca(2+) dependence. Given the fact that multiple pore residues in BK displayed side-chain hydrophilicity-dependent constitutive openness, we propose that BK channel opening involves structural rearrangement of the deep-pore region, where multiple residues undergo conformational changes that may increase the exposure of their side chains to the polar environment of the pore.

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Citations

Apr 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Yu ZhouChristopher J Lingle
Oct 29, 2014·The Journal of General Physiology·Yu Zhou, Christopher J Lingle
Jul 29, 2015·The Journal of General Physiology·Jon T Sack, Drew C Tilley
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Jun 15, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jiusheng YanRichard W Aldrich
Nov 17, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yutao TianToshinori Hoshi
Oct 14, 2017·The Journal of General Physiology·Yu ZhouChristopher J Lingle
Nov 4, 2016·Physiological Reviews·Ramon LatorreOsvaldo Alvarez
Mar 2, 2017·The Journal of General Physiology·Teresa Giraldez, Brad S Rothberg
Apr 11, 2019·Proceedings of the National Academy of Sciences of the United States of America·Yutao TianToshinori Hoshi
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Apr 25, 2021·BMC Bioinformatics·Makros N XenakisHubert J Smeets

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