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Structural insights into light-gating of potassium-selective channelrhodopsin

Author

Listed:
  • Takefumi Morizumi

    (University of Toronto)

  • Kyumhyuk Kim

    (University of Toronto)

  • Hai Li

    (The University of Texas Health Science Center at Houston McGovern Medical School)

  • Probal Nag

    (The Hebrew University of Jerusalem
    Technical University Dortmund)

  • Tal Dogon

    (The Hebrew University of Jerusalem)

  • Oleg A. Sineshchekov

    (The University of Texas Health Science Center at Houston McGovern Medical School)

  • Yumei Wang

    (The University of Texas Health Science Center at Houston McGovern Medical School)

  • Leonid S. Brown

    (University of Guelph)

  • Songhwan Hwang

    (Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP))

  • Han Sun

    (Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP)
    Technical University of Berlin)

  • Ana-Nicoleta Bondar

    (University of Bucharest
    Forschungszentrum Jülich)

  • Igor Schapiro

    (The Hebrew University of Jerusalem
    Technical University Dortmund)

  • Elena G. Govorunova

    (The University of Texas Health Science Center at Houston McGovern Medical School)

  • John L. Spudich

    (The University of Texas Health Science Center at Houston McGovern Medical School)

  • Oliver P. Ernst

    (University of Toronto
    University of Toronto)

Abstract

Structural information on channelrhodopsins’ mechanism of light-gated ion conductance is scarce, limiting its engineering as optogenetic tools. Here, we use single-particle cryo-electron microscopy of peptidisc-incorporated protein samples to determine the structures of the slow-cycling mutant C110A of kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) in the dark and upon laser flash excitation. Upon photoisomerization of the retinal chromophore, the retinylidene Schiff base NH-bond reorients from the extracellular to the cytoplasmic side. This switch triggers a series of side chain reorientations and merges intramolecular cavities into a transmembrane K+ conduction pathway. Molecular dynamics simulations confirm K+ flux through the illuminated state but not through the resting state. The overall displacement between the closed and the open structure is small, involving mainly side chain rearrangements. Asp105 and Asp116 play a key role in K+ conductance. Structure-guided mutagenesis and patch-clamp analysis reveal the roles of the pathway-forming residues in channel gating and selectivity.

Suggested Citation

  • Takefumi Morizumi & Kyumhyuk Kim & Hai Li & Probal Nag & Tal Dogon & Oleg A. Sineshchekov & Yumei Wang & Leonid S. Brown & Songhwan Hwang & Han Sun & Ana-Nicoleta Bondar & Igor Schapiro & Elena G. Gov, 2025. "Structural insights into light-gating of potassium-selective channelrhodopsin," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56491-9
    DOI: 10.1038/s41467-025-56491-9
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    References listed on IDEAS

    as
    1. Jörg Standfuss & Patricia C. Edwards & Aaron D’Antona & Maikel Fransen & Guifu Xie & Daniel D. Oprian & Gebhard F. X. Schertler, 2011. "The structural basis of agonist-induced activation in constitutively active rhodopsin," Nature, Nature, vol. 471(7340), pages 656-660, March.
    2. Stanislav Ott & Sangyu Xu & Nicole Lee & Ivan Hong & Jonathan Anns & Danesha Devini Suresh & Zhiyi Zhang & Xianyuan Zhang & Raihanah Harion & Weiying Ye & Vaishnavi Chandramouli & Suresh Jesuthasan & , 2024. "Kalium channelrhodopsins effectively inhibit neurons," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Hui-Woog Choe & Yong Ju Kim & Jung Hee Park & Takefumi Morizumi & Emil F. Pai & Norbert Krauß & Klaus Peter Hofmann & Patrick Scheerer & Oliver P. Ernst, 2011. "Crystal structure of metarhodopsin II," Nature, Nature, vol. 471(7340), pages 651-655, March.
    4. 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.
    5. Stanislav Ott & Sangyu Xu & Nicole Lee & Ivan Hong & Jonathan Anns & Danesha Devini Suresh & Zhiyi Zhang & Xianyuan Zhang & Raihanah Harion & Weiying Ye & Vaishnavi Chandramouli & Suresh Jesuthasan & , 2024. "Author Correction: Kalium channelrhodopsins effectively inhibit neurons," Nature Communications, Nature, vol. 15(1), pages 1-1, December.
    6. 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.
    7. 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.
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