The push-to-open mechanism of the tethered mechanosensitive ion channel NompC.
The push-to-open mechanism of the tethered mechanosensitive ion channel NompC.
复制标题
系留机械敏感离子通道 NompC 的推开机制
作者：
Wang Y;Guo Y;Li G;Liu C;Wang L;Zhang A;Yan Z;Song C
NompC是果蝇中负责触觉和平衡感觉的机械敏感离子通道。基于解析的cryo-EM结构，我们进行了全原子分子动力学模拟和电生理实验来研究NompC门控的原子细节。我们的研究结果表明，NompC可以通过压缩细胞内锚蛋白重复结构域而不是通过拉伸打开，并且沿着力传递途径的大量氢键沿着对于机械敏感性是重要的。在细胞内压缩下，成束的锚蛋白重复序列区就像弹簧一样，以约1.8 nm ps−1的速率传递力，弹簧常数约为13 pN nm−1。接头螺旋区作为锚蛋白重复序列和瞬时受体电位（TRP）结构域之间的桥梁，其将推力传递到TRP结构域以进行顺时针旋转，导致通道打开。这可能是类似的拴系机械敏感性TRP通道的通用门控机制，其使细胞能够感觉到压缩和收缩。
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.