| Author |
Liu, Hao-wen Ding, Jiu-ping Zhao, Zhi-wen Hu, Bin Wang, Lu-yang Hou, Pan-pan Li, Xia Guo, Xi-ying Wang, Sheng |
| Description |
Author Affiliation: Liu HW ( From the 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 and.); Hou PP ( From the 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 and.); Guo XY ( From the 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 and.); Zhao ZW ( From the 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 and.); Hu B ( From the 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 and.); Li X ( From the 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 and.); Wang LY ( the Program in Neurosciences and Mental Health, SickKids Research Institute and Department of Physiology, University of Toronto, Toronto, Ontario M5G 1X8, Canada.); Ding JP ( From the 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 and jpding@mail.hust.edu.cn.); Wang S ( From the 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 and shengwang@mail.hust.edu.cn.) |
| Abstract |
Large conductance Ca(2+)- and voltage-activated potassium (BK) channels, composed of pore-forming subunits and auxiliary ß subunits, play important roles in diverse physiological activities. The ß1 is predominately expressed in smooth muscle cells, where it greatly enhances the Ca(2+) sensitivity of BK channels for proper regulation of smooth muscle tone. However, the structural basis underlying dynamic interaction between BK mSlo1 and ß1 remains elusive. Using macroscopic ionic current recordings in various Ca(2+) and Mg(2+) concentrations, we identified two binding sites on the cytosolic N terminus of ß1, namely the electrostatic enhancing site (mSlo1(K392,R393)-ß1(E13,T14)), increasing the calcium sensitivity of BK channels, and the hydrophobic site (mSlo1(L906,L908)-ß1(L5,V6,M7)), passing the physical force from the Ca(2+) bowl onto the enhancing site and S6 C-linker. Dynamic binding of these sites affects the interaction between the cytosolic domain and voltage-sensing domain, leading to the reduction of Mg(2+) sensitivity. A comprehensive structural model of the BK(mSlo1 -ß1) complex was reconstructed based on these functional studies, which provides structural and mechanistic insights for understanding BK gating. |
