Cryo-EM structure of the open high-conductance Ca2+-activated K+ channel

• Published in: Nature (London) Vol. 541; no. 7635; pp. 46 - 51
• Main Authors: Tao, Xiao, Hite, Richard K., MacKinnon, Roderick
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.01.2017; Nature Publishing Group
• Subjects: 631/45/269/1151; 631/535/1258/1259; 631/57/2270/1140; Calcium binding proteins; Humanities and Social Sciences; Methods; multidisciplinary; Physiological aspects; Potassium channels; Protein structure prediction; Science
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/nature20608

The Ca 2+ -activated K + channel, Slo1, has an unusually large conductance and contains a voltage sensor and multiple chemical sensors. Dual activation by membrane voltage and Ca 2+ renders Slo1 central to processes that couple electrical signalling to Ca 2+ -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 Ca 2+ and Mg 2+ 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 Ca 2+ -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 Ca 2+ ions, in which an unconventional allosteric voltage-sensing mechanism regulates the Ca 2+ sensor in addition to the voltage sensor’s direct action on the pore. Slo1 potassium channel structure and activity 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 Ca 2+ ions, suggesting an unconventional allosteric mechanism, whereby the voltage sensor regulates the Ca 2+ 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.