TY - JOUR
T1 - BK channel opening involves side-chain reorientation of multiple deep-pore residues
AU - Chen, Xixi
AU - Yan, Jiusheng
AU - Aldrich, Richard W.
PY - 2014
Y1 - 2014
N2 - Three deep-pore locations, L312, A313, and A316, were identified in a scanning mutagenesis study of the BK (Ca2+-activated, largeconductance 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.
AB - Three deep-pore locations, L312, A313, and A316, were identified in a scanning mutagenesis study of the BK (Ca2+-activated, largeconductance 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.
KW - Gating
KW - Ion channel pore
KW - Structure-function
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U2 - 10.1073/pnas.1321697111
DO - 10.1073/pnas.1321697111
M3 - Article
C2 - 24367115
AN - SCOPUS:84891928761
SN - 0027-8424
VL - 111
SP - E79-E88
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -