Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine.
Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine.
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DOI：
10.1016/j.cell.2022.01.007
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发表时间：
2022-02-17
期刊：
影响因子：
64.5
通讯作者：
Kato HE
中科院分区：
文献类型：
--
作者：
Kishi KE;Kim YS;Fukuda M;Inoue M;Kusakizako T;Wang PY;Ramakrishnan C;Byrne EFX;Thadhani E;Paggi JM;Matsui TE;Yamashita K;Nagata T;Konno M;Quirin S;Lo M;Benster T;Uemura T;Liu K;Shibata M;Nomura N;Iwata S;Nureki O;Dror RO;Inoue K;Deisseroth K;Kato HE
ChRmine是最近发现的一种泵浦样阳离子传导通道-视紫红质，它具有令人费解的性质(大的光电流、红移的光谱和极高的光敏感度)，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，但从初级序列来看，更类似于离子泵视紫红质；在这个家族中，被动通道传导的机制仍然是个谜。在这里，我们展示了ChRmine的2.0？分辨率低温EM结构，揭示了通道视紫红质的非典型结构特征：三聚体组装，一个短的跨膜螺旋3，一个扭曲的细胞外环1，单体内的大前庭，以及三聚体界面上的开口。我们应用这种结构设计了三种蛋白质(rsChRmine和hsChRmine，分别赋予了进一步的红移和高速特性，以及frChRmine，结合了更快和更红移的性能)，适合于基础神经科学的机会。这些结果阐明了泵状通道视紫红质的传导和门控，并为进一步在结构指导下创建跨生物学应用的通道视紫红质指明了方向。
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 Å 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.
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影响因子：
3.7
作者：
Chan SK;Kitajima-Ihara T;Fujii R;Gotoh T;Murakami M;Ihara K;Kouyama T
通讯作者：
Kouyama T
影响因子：
46.9
作者：
Chen R;Gore F;Nguyen QA;Ramakrishnan C;Patel S;Kim SH;Raffiee M;Kim YS;Hsueh B;Krook-Magnusson E;Soltesz I;Deisseroth K
通讯作者：
Deisseroth K
影响因子：
62.1
作者：
Ernst, Oliver P.;Lodowski, David T.;Elstner, Marcus;Hegemann, Peter;Brown, Leonid S.;Kandori, Hideki
通讯作者：
Kandori, Hideki
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
2.9
作者：
BRAIMAN, MS;MOGI, T;ROTHSCHILD, KJ
通讯作者：
ROTHSCHILD, KJ