Inter-α/β Subunits Coupling Mediating Pre-inactivation and Augmented Activation of BKCa(β2)

Overview

Journal Sci Rep

Specialty Science

Date 2013 Apr 17

PMID 23588888

Citations 14

Authors

Panpan Hou

Wenping Zeng

Geliang Gan

Caixia Lv

Xiying Guo

Zheng Zhang

Haowen Liu

Ying Wu

Jing Yao

Aguan D Wei

Sheng Wang

Jiuping Ding

Affiliations

Soon will be listed here.

Abstract

Large-conductance calcium-activated potassium (BK) channels regulate the electric properties and neurotransmitter release in excitable cells. Its auxiliary β2 subunits not only enhance gating, but also confer inactivation via a short-lived preinactivated state. However, the mechanism of enhancement and preinactivation of BK channels by β2 remains elusive. Using our newly developed methods, we demonstrated that electrostatic forces played a crucial role in forming multiple complementary pairs of binding sites between α and β subunits including a "PI site" required for channel preinactivation, an "E site" enhancing calcium sensitivity and an "ECaB" coupling site transferring force to gate from the Ca(2+)-bowl via the β2(K33, R34, K35), E site and S6-C linker, independent of another Ca(2+) binding site mSlo1(D362,D367). A comprehensive structural model of the BK(β2) complex was reconstructed based on these functional studies, which paves the way for a clearer understanding of the structural mechanisms of activation and preinactivation of other BK(β) complexes.

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