Kuang Yaming Honors School, Nanjing University, Nanjing 210023, People's Republic of China; Institute for Brain Sciences, Nanjing University, Nanjing 210023, People's Republic of China; Corresponding author
Yiming Zhang
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, People's Republic of China
Ruiheng Song
Kuang Yaming Honors School, Nanjing University, Nanjing 210023, People's Republic of China
Jingjie Xu
State Key Laboratory of Scientific and Engineering Computing, National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, People's Republic of China
Yigao Yuan
Kuang Yaming Honors School, Nanjing University, Nanjing 210023, People's Republic of China
Jindou Liu
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, People's Republic of China
Jia Li
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, People's Republic of China
Sisi Zheng
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, People's Republic of China
Tiantian Liu
State Key Laboratory of Scientific and Engineering Computing, National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, People's Republic of China; CAEP Software Center for High Performance Numerical Simulation, Beijing 100088, People's Republic of China
Benzhuo Lu
State Key Laboratory of Scientific and Engineering Computing, National Center for Mathematics and Interdisciplinary Sciences, Academy of Mathematics and Systems Science, Chinese Academy of Sciences, Beijing 100190, People's Republic of China; Corresponding author
Youjun Wang
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, People's Republic of China; Corresponding author
Michael L. Klein
Institute for Computational Molecular Science, Temple University, Philadelphia, PA 19122, USA; Corresponding author
Summary: Store-operated calcium release-activated calcium (CRAC) channels mediate a variety of cellular signaling functions. The CRAC channel pore-forming protein, Orai1, is a hexamer arranged with 3-fold symmetry. Despite its importance in moving Ca2+ ions into cells, a detailed mechanistic understanding of Orai1 activation is lacking. Herein, a working model is proposed for the putative open state of Orai from Drosophila melanogaster (dOrai), which involves a “twist-to-open” gating mechanism. The proposed model is supported by energetic, structural, and experimental evidence. Fluorescent imaging demonstrates that each subunit on the intracellular side of the pore is inherently strongly cross-linked, which is important for coupling to STIM1, the pore activator, and graded activation of the Orai1 channel. The proposed model thus paves the way for understanding key aspects of calcium signaling at a molecular level. : Biological Sciences; Molecular Biology; Structural Biology Subject Areas: Biological Sciences, Molecular Biology, Structural Biology
