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Abstract
The Ca2+-activated K+ channel, Slo1, has an unusually large conductance and contains a voltage sensor and multiple chemical sensors. Dual activation by membrane voltage and Ca2+ renders Slo1 central to processes that couple electrical signalling to Ca2+-mediated events such as muscle contraction and neuronal excitability. Here we present the cryo-electron microscopy structure of a full-length Slo1 channel from Aplysia californica in the presence of Ca2+ and Mg2+ at a resolution of 3.5 Å. The channel adopts an open conformation. Its voltage-sensor domain adopts a non-domain-swapped attachment to the pore and contacts the cytoplasmic Ca2+-binding domain from a neighbouring subunit. Unique structural features of the Slo1 voltage sensor suggest that it undergoes different conformational changes than other known voltage sensors. The structure reveals the molecular details of three distinct divalent cation-binding sites identified through electrophysiological studies of mutant Slo1 channels. Two complementary studies present the full-length high-resolution structure of a Slo1 channel in the presence or absence of Ca2+ ions, in which an unconventional allosteric voltage-sensing mechanism regulates the Ca2+ sensor in addition to the voltage sensor’s direct action on the pore. Dual activation by voltage and calcium ions makes Slo1/BK channels essential to processes that couple membrane electrical excitability and cellular calcium signalling, such as muscle contraction or neuronal communication. In two complementary studies, Roderick MacKinnon and colleagues present full-length structures for a Slo1 channel, either in the presence or the absence of Ca2+ ions, suggesting an unconventional allosteric mechanism, whereby the voltage sensor regulates the Ca2+ sensor instead of the channel's pore directly. These findings explain a large body of biochemical, genetic and physiological data, from both basic and clinical research.Cite this article
Tao, X., Hite, R. & MacKinnon, R. Cryo-EM structure of the open high-conductance Ca2+-activated K+ channel. Nature 541, 46–51 (2017). https://doi.org/10.1038/nature20608 