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Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs

Author

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  • Kyle Tucker

    (University of California Berkeley
    University of California Berkeley
    University of California)

  • Savitha Sridharan

    (University of California Berkeley
    University of California Berkeley)

  • Hillel Adesnik

    (University of California Berkeley
    University of California Berkeley)

  • Stephen G. Brohawn

    (University of California Berkeley
    University of California Berkeley
    University of California)

Abstract

Microbial channelrhodopsins are light-gated ion channels widely used for optogenetic manipulation of neuronal activity. ChRmine is a bacteriorhodopsin-like cation channelrhodopsin (BCCR) more closely related to ion pump rhodopsins than other channelrhodopsins. ChRmine displays unique properties favorable for optogenetics including high light sensitivity, a broad, red-shifted activation spectrum, cation selectivity, and large photocurrents, while its slow closing kinetics impedes some applications. The structural basis for ChRmine function, or that of any other BCCR, is unknown. Here, we present cryo-EM structures of ChRmine in lipid nanodiscs in apo (opsin) and retinal-bound (rhodopsin) forms. The structures reveal an unprecedented trimeric architecture with a lipid filled central pore. Large electronegative cavities on either side of the membrane facilitate high conductance and selectivity for cations over protons. The retinal binding pocket structure suggests channel properties could be tuned with mutations and we identify ChRmine variants with ten-fold decreased and two-fold increased closing rates. A T119A mutant shows favorable properties relative to wild-type and previously reported ChRmine variants for optogenetics. These results provide insight into structural features that generate an ultra-potent microbial opsin and provide a platform for rational engineering of channelrhodopsins with improved properties that could expand the scale, depth, and precision of optogenetic experiments.

Suggested Citation

  • Kyle Tucker & Savitha Sridharan & Hillel Adesnik & Stephen G. Brohawn, 2022. "Cryo-EM structures of the channelrhodopsin ChRmine in lipid nanodiscs," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32441-7
    DOI: 10.1038/s41467-022-32441-7
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    1. Takanori Matsubara & Takayuki Yanagida & Noriaki Kawaguchi & Takashi Nakano & Junichiro Yoshimoto & Maiko Sezaki & Hitoshi Takizawa & Satoshi P. Tsunoda & Shin-ichiro Horigane & Shuhei Ueda & Sayaka T, 2021. "Remote control of neural function by X-ray-induced scintillation," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
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    3. Kazumasa Oda & Johannes Vierock & Satomi Oishi & Silvia Rodriguez-Rozada & Reiya Taniguchi & Keitaro Yamashita & J. Simon Wiegert & Tomohiro Nishizawa & Peter Hegemann & Osamu Nureki, 2018. "Crystal structure of the red light-activated channelrhodopsin Chrimson," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    4. Hideaki E. Kato & Motoshi Kamiya & Seiya Sugo & Jumpei Ito & Reiya Taniguchi & Ayaka Orito & Kunio Hirata & Ayumu Inutsuka & Akihiro Yamanaka & Andrés D. Maturana & Ryuichiro Ishitani & Yuki Sudo & Sh, 2015. "Atomistic design of microbial opsin-based blue-shifted optogenetics tools," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
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    1. Yuanyue Shan & Liping Zhao & Meiyu Chen & Xiao Li & Mingfeng Zhang & Duanqing Pei, 2024. "Channelrhodopsins with distinct chromophores and binding patterns," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    2. Takefumi Morizumi & Kyumhyuk Kim & Hai Li & Elena G. Govorunova & Oleg A. Sineshchekov & Yumei Wang & Lei Zheng & Éva Bertalan & Ana-Nicoleta Bondar & Azam Askari & Leonid S. Brown & John L. Spudich &, 2023. "Structures of channelrhodopsin paralogs in peptidiscs explain their contrasting K+ and Na+ selectivities," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. T. Bertie Ansell & Wanling Song & Claire E. Coupland & Loic Carrique & Robin A. Corey & Anna L. Duncan & C. Keith Cassidy & Maxwell M. G. Geurts & Tim Rasmussen & Andrew B. Ward & Christian Siebold & , 2023. "LipIDens: simulation assisted interpretation of lipid densities in cryo-EM structures of membrane proteins," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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