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Inter-α/β subunits coupling mediating pre-inactivation and augmented activation of BKCa(β2)
Panpan Hou1, Wenping Zeng, Geliang Gan
1Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China.
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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