한빛사 논문
Koichiro E. Kishi1,17, Yoon Seok Kim2,17, Masahiro Fukuda1,17, Masatoshi Inoue2,17, Tsukasa Kusakizako3,17, Peter Y. Wang2,17, Charu Ramakrishnan4, Eamon F.X.Byrne2, Elina Thadhani2,5, Joseph M. Paggi5, Toshiki E. Matsui1, Keitaro Yamashita6, Takashi Nagata7,8, Masae Konno7,8, Sean Quirin2, Maisie Lo2, Tyler Benster2, Tomoko Uemura9, Kehong Liu9, Mikihiro Shibata10,11, Norimichi Nomura9, So Iwata9,12, Osamu Nureki3, Ron O. Dror5,13, Keiichi Inoue7, Karl Deisseroth2,4,14,15,18,*, Hideaki E. Kato1,3,8,16,*
1Komaba Institute for Science, The University of Tokyo, Meguro, Tokyo, Japan
2Department of Bioengineering, Stanford University, Stanford, CA, USA
3Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo, Tokyo, Japan
4CNC Program, Stanford University, Palo Alto, CA, USA
5Department of Computer Science, Stanford University, Stanford, CA, USA
6MRC Laboratory of Molecular Biology, Cambridge Biomedical Campus, Cambridge, UK
7Institute for Solid State Physics, The University of Tokyo, Kashiwa, Japan
8PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan
9Department of Cell Biology, Graduate School of Medicine, Kyoto University, Kyoto, Sakyo, Japan
10WPI Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma, Kanazawa, Japan
11High-Speed AFM for Biological Application Unit, Institute for Frontier Science Initiative, Kanazawa University, Kakuma, Kanazawa, Japan
12RIKEN SPring-8 Center, Kouto, Sayo-cho, Sayo-gun, Hyogo, Japan
13Institute for Computational and Mathematical Engineering, Stanford University, Stanford, CA, USA
14Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA
15Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA
16FOREST, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan
17These authors contributed equally
18Lead contact
*Corresponding author
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 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.
Keywords : channelrhodopsin, optogenetics, microbial opsin, all-optical, ChRmine, cryo-EM, structure-guided engineering, pump-like channelrhodopsin, PLCR
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