An allosteric modulator activates BK channels by perturbing coupling between Ca2+ binding and pore opening

Guohui Zhang; Xianjin Xu; Zhiguang Jia; Yanyan Geng; Hongwu Liang; Jingyi Shi; Martina Marras; Carlota Abella; Karl L. Magleby; Jonathan R. Silva; Jianhan Chen; Xiaoqin Zou; Jianmin Cui

doi:10.1038/s41467-022-34359-6

Nature Communications (Nov 2022)

An allosteric modulator activates BK channels by perturbing coupling between Ca2+ binding and pore opening

Guohui Zhang,
Xianjin Xu,
Zhiguang Jia,
Yanyan Geng,
Hongwu Liang,
Jingyi Shi,
Martina Marras,
Carlota Abella,
Karl L. Magleby,
Jonathan R. Silva,
Jianhan Chen,
Xiaoqin Zou,
Jianmin Cui

Affiliations

Guohui Zhang: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University
Xianjin Xu: Dalton Cardiovascular Research Center, University of Missouri – Columbia
Zhiguang Jia: Department of Chemistry, University of Massachusetts
Yanyan Geng: Department of Physiology and Biophysics, University of Miami Miller School of Medicine
Hongwu Liang: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University
Jingyi Shi: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University
Martina Marras: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University
Carlota Abella: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University
Karl L. Magleby: Department of Physiology and Biophysics, University of Miami Miller School of Medicine
Jonathan R. Silva: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University
Jianhan Chen: Department of Chemistry, University of Massachusetts
Xiaoqin Zou: Dalton Cardiovascular Research Center, University of Missouri – Columbia
Jianmin Cui: Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Disorders, Cardiac Bioelectricity and Arrhythmia Center, Washington University

DOI: https://doi.org/10.1038/s41467-022-34359-6
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 13

Abstract

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Ca2+ activated BK channels are important for neural and muscle function. Here authors use a compound, BC5, to show that the interface between the cytosolic and voltage sensing domains is a major allosteric pathway for Ca2+ binding to open the channel.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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