小柯机器人

日本东京大学Hideaki E. Kato、美国斯坦福大学Karl Deisseroth等研究人员合作揭示泵状光敏感通道蛋白ChRmine通道传导的结构基础。2022年2月2日，《细胞》杂志在线发表了这项成果。

研究人员报道了ChRmine 2.0 Å分辨率的冷冻电镜结构，从而揭示了光敏感通道蛋白的非典型结构特征：三聚体组装，一个短的跨膜螺旋，一个扭曲的细胞外环，单体内的大前庭，以及三聚体接口处的开口。研究人员应用这一结构设计了三种适合基础神经科学研究的蛋白质（rsChRmine和hsChRmine，分别实现进一步的红移和高速性能，以及frChRmine，结合更快和更红移的性能）。这些结果阐明了泵类通道光合蛋白的传导和门控，并为进一步在结构指导下创造通道光合蛋白在整个生物学领域的应用指明了方向。

据悉，ChRmine是最近发现的一种类似于泵的阳离子传导光敏感通道蛋白，表现出令人费解的特性（大的光电流、红移光谱和极端的光敏感性），为光遗传学创造了新的机会。ChRmine及其同系物具有离子通道的功能，但从主要序列来看，更接近于离子泵光敏感通道蛋白；该家族的被动通道传导机制一直很神秘。

附：英文原文

Title: Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine

Author: Koichiro E. Kishi, Yoon Seok Kim, Masahiro Fukuda, Masatoshi Inoue, Tsukasa Kusakizako, Peter Y. Wang, Charu Ramakrishnan, Eamon F.X. Byrne, Elina Thadhani, Joseph M. Paggi, Toshiki E. Matsui, Keitaro Yamashita, Takashi Nagata, Masae Konno, Sean Quirin, Maisie Lo, Tyler Benster, Tomoko Uemura, Kehong Liu, Mikihiro Shibata, Norimichi Nomura, So Iwata, Osamu Nureki, Ron O. Dror, Keiichi Inoue, Karl Deisseroth, Hideaki E. Kato

Issue&Volume: 2022-02-03

Abstract: ChRmine, a recently discovered pump-like cation-conducting channelrhodopsin, exhibits puzzling properties (large photocurrents, red-shifted spectrum, and extreme light sensitivity) that have created new opportunities in optogenetics. ChRmine and its homologs function as ion channels but, by primary sequence, more closely resemble ion pump rhodopsins; mechanisms for passive channel conduction in this family have remained mysterious. Here, we present the 2.0 resolution cryo-EM structure of ChRmine, revealing architectural features atypical for channelrhodopsins: trimeric assembly, a short transmembrane-helix 3, a twisting extracellular-loop 1, large vestibules within the monomer, and an opening at the trimer interface. We applied this structure to design three proteins (rsChRmine and hsChRmine, conferring further red-shifted and high-speed properties, respectively, and frChRmine, combining faster and more red-shifted performance) suitable for fundamental neuroscience opportunities. These results illuminate the conduction and gating of pump-like channelrhodopsins and point the way toward further structure-guided creation of channelrhodopsins for applications across biology.

DOI: 10.1016/j.cell.2022.01.007

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00031-9