德国哥廷根大学Martin C. Göpfert研究组发现，NOMPC离子通道铰链形成一个门控弹簧来启动机械感知。2025年1月6日，《自然—神经科学》杂志在线发表了这项成果。

通过将蛋白质结构域重复、机械测量、电生理学、分子动力学模拟和建模相结合，研究人员识别出NOMPC门控弹簧是锚定蛋白连接物与通道门之间的短连接物。这个连接物充当一个胡克铰链，其弹性是连接物的十倍，且铰链决定了通道的门控和门控弹簧的固有刚度。

该研究揭示了机械感知如何在分子层面上启动，解开了门控弹簧和连接物的关系，以及各自的通道门控范式；并提出门控弹簧作为核心离子通道成分，能够通过多种刺激在各种通道中实现高效门控。

据悉，机械刺激的感觉是由弹性门控弹簧启动的，这些弹簧拉开机械感觉转导通道。对门控弹簧的研究集中于传递力的蛋白质连接物，例如果蝇机械感觉转导通道NOMPC的氨基端锚定蛋白连接物。

附：英文原文

Title: NOMPC ion channel hinge forms a gating spring that initiates mechanosensation

Author: Hehlert, Philip, Effertz, Thomas, Gu, Ruo-Xu, Nadrowski, Bjrn, Geurten, Bart R. H., Beutner, Dirk, de Groot, Bert L., Gpfert, Martin C.

Issue&Volume: 2025-01-06

Abstract: The sensation of mechanical stimuli is initiated by elastic gating springs that pull open mechanosensory transduction channels. Searches for gating springs have focused on force-conveying protein tethers such as the amino-terminal ankyrin tether of the Drosophila mechanosensory transduction channel NOMPC. Here, by combining protein domain duplications with mechanical measurements, electrophysiology, molecular dynamics simulations and modeling, we identify the NOMPC gating-spring as the short linker between the ankyrin tether and the channel gate. This linker acts as a Hookean hinge that is ten times more elastic than the tether, with the linker hinge dictating channel gating and the intrinsic stiffness of the gating spring. Our study shows how mechanosensation is initiated molecularly; disentangles gating springs and tethers, and respective paradigms of channel gating; and puts forward gating springs as core ion channel constituents that enable efficient gating by diverse stimuli and in a wide variety of channels.

DOI: 10.1038/s41593-024-01849-3

Source: https://www.nature.com/articles/s41593-024-01849-3