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Structures of channelrhodopsin paralogs in peptidiscs explain their contrasting K+ and Na+ selectivities

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)

  • Elena G. Govorunova

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

  • 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)

  • Lei Zheng

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

  • Éva Bertalan

    (RWTH-Aachen University)

  • Ana-Nicoleta Bondar

    (University of Bucharest
    Institute of Computational Biomedicine (IAS-5/INM-9), Forschungszentrum Jülich)

  • Azam Askari

    (University of Guelph)

  • Leonid S. Brown

    (University of Guelph)

  • 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

Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is a light-gated channel used for optogenetic silencing of mammalian neurons. It selects K+ over Na+ in the absence of the canonical tetrameric K+ selectivity filter found universally in voltage- and ligand-gated channels. The genome of H. catenoides also encodes a highly homologous cation channelrhodopsin (HcCCR), a Na+ channel with >100-fold larger Na+ to K+ permeability ratio. Here, we use cryo-electron microscopy to determine atomic structures of these two channels embedded in peptidiscs to elucidate structural foundations of their dramatically different cation selectivity. Together with structure-guided mutagenesis, we show that K+ versus Na+ selectivity is determined at two distinct sites on the putative ion conduction pathway: in a patch of critical residues in the intracellular segment (Leu69/Phe69, Ile73/Ser73 and Asp116) and within a cluster of aromatic residues in the extracellular segment (primarily, Trp102 and Tyr222). The two filters are on the opposite sides of the photoactive site involved in channel gating.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40041-2
    DOI: 10.1038/s41467-023-40041-2
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    References listed on IDEAS

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    Cited by:

    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.

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