Twist is the key to the gating of mechanosensitive ion channel NOMPC

NOMPC, a tethered mechanosensitive ion channel from the transient receptor potential (TRP) family, can convert mechanical stimuli to ionic electric signals to excite neuron cells. Previous investigations revealed that a pushing force exerted on the linker helix domain or the compression of NOMPC’s ankyrin repeat (AR) domain triggers channel opening. In this study, we explored the direct mechanical cause for NOMPC channel opening as well as the torsional properties of the AR domain using all-atom molecular dynamics simulations. Our results demonstrate that a torque pointing toward the extracellular side, exerted on the amphipathic TRP domain, serves as the direct cause of driving the channel open. The coupling between the compression and twisting of the AR domain ensures that both types of deformations can open the channel. Therefore, we propose a twist-to-open model, facilitated by the compression-twist coupling property of the AR domain, to further elucidate the gating mechanism of the NOMPC channel.