The push-to-open mechanism of the tethered mechanosensitive ion channel NompC

eLife

Lei Wang¹  Chunhong Liu¹  Yang Wang²  Aihua Zhang²  Chen Song²  Yifeng Guo³  Zhiqiang Yan⁴  Guanluan Li⁴ 

[1] Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China;Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China;Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China;State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science, School of Life Sciences, Fudan University, Shanghai, China;State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science, School of Life Sciences, Fudan University, Shanghai, China;Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China;

关键词: NompC;    mechanosensitive ion channel;    molecular dynamics;    electrophysiology;    gating;    D. melanogaster;   

DOI  :  10.7554/eLife.58388

来源: eLife Sciences Publications, Ltd

【 摘 要 】

NompC is a mechanosensitive ion channel responsible for the sensation of touch and balance in Drosophila melanogaster. Based on a resolved cryo-EM structure, we performed all-atom molecular dynamics simulations and electrophysiological experiments to study the atomistic details of NompC gating. Our results showed that NompC could be opened by compression of the intracellular ankyrin repeat domain but not by a stretch, and a number of hydrogen bonds along the force convey pathway are important for the mechanosensitivity. Under intracellular compression, the bundled ankyrin repeat region acts like a spring with a spring constant of ~13 pN nm−1 by transferring forces at a rate of ~1.8 nm ps−1. The linker helix region acts as a bridge between the ankyrin repeats and the transient receptor potential (TRP) domain, which passes on the pushing force to the TRP domain to undergo a clockwise rotation, resulting in the opening of the channel. This could be the universal gating mechanism of similar tethered mechanosensitive TRP channels, which enable cells to feel compression and shrinkage.

【 授权许可】

CC BY