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Regulatory ?1 subunits defy symmetry in functional modulation of BK channels.


ABSTRACT: Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory regulatory proteins can also critically define the precise functional role of such channels. For instance, the pore-forming subunit of the large conductance voltage and calcium-activated potassium (BK, Slo1, or KCa1.1) channels encoded by a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional diversity arises from two families of regulatory subunits, ? and ?, which help define the range of voltages over which BK channels in a given cell are activated, thereby defining physiological roles. A BK channel can contain zero to four ? subunits per channel, with each ? subunit incrementally influencing channel gating behavior, consistent with symmetry expectations. In contrast, a ?1 subunit (or single type of ?1 subunit complex) produces a functionally all-or-none effect, but the underlying stoichiometry of ?1 assembly and function remains unknown. Here we utilize two distinct and independent methods, a Forster resonance energy transfer-based optical approach and a functional reporter in single-channel recordings, to reveal that a BK channel can contain up to four ?1 subunits, but a single ?1 subunit suffices to induce the full gating shift. This requires that the asymmetric association of a single regulatory protein can act in a highly concerted fashion to allosterically influence conformational equilibria in an otherwise symmetric K+ channel.

SUBMITTER: Gonzalez-Perez V 

PROVIDER: S-EPMC6176617 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Regulatory γ1 subunits defy symmetry in functional modulation of BK channels.

Gonzalez-Perez Vivian V   Ben Johny Manu M   Xia Xiao-Ming XM   Lingle Christopher J CJ  

Proceedings of the National Academy of Sciences of the United States of America 20180917 40


Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory regulatory proteins can also critically define the precise functional role of such channels. For instance, the pore-forming subunit of the large conductance voltage and calcium-activated potassium (BK, Slo1, or KCa<sub>1.1</sub>) channels encoded by a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional diversity arises from two families of regulatory subunits, β and γ, which help define the range of v  ...[more]

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