title: Inter-α/β subunits coupling mediating pre-inactivation and augmented activation of BKCa(β2).
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.
authors.affiliation: Key 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.
authors.forename: Panpan
authors.initials: P
authors.lastname: Hou
authors.forename: Wenping
authors.initials: W
authors.lastname: Zeng
authors.forename: Geliang
authors.initials: G
authors.lastname: Gan
authors.forename: Caixia
authors.initials: C
authors.lastname: Lv
authors.forename: Xiying
authors.initials: X
authors.lastname: Guo
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Haowen
authors.initials: H
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Aguan D
authors.initials: AD
authors.lastname: Wei
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.forename: Jiuping
authors.initials: J
authors.lastname: Ding
mesh_terms: D002118:Calcium / Q000737:chemistry*; D003198:Computer Simulation; D015640:Ion Channel Gating; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry* / Q000648:ultrastructure*; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits; D055672:Static Electricity
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D021122:Protein Subunits; D002118:Calcium