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


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.

SUBMITTER: Chen X 

PROVIDER: S-EPMC3890798 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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

Chen Xixi X   Yan Jiusheng J   Aldrich Richard W RW  

Proceedings of the National Academy of Sciences of the United States of America 20131223 1


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 th  ...[more]

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