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Structure of a mammalian sperm cation channel complex

Author

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  • Shiyi Lin

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Institute of Biology, Westlake Institute for Advanced Study)

  • Meng Ke

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Institute of Biology, Westlake Institute for Advanced Study)

  • Yuqi Zhang

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Institute of Biology, Westlake Institute for Advanced Study)

  • Zhen Yan

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Institute of Biology, Westlake Institute for Advanced Study)

  • Jianping Wu

    (Westlake University
    Westlake Laboratory of Life Sciences and Biomedicine
    Institute of Biology, Westlake Institute for Advanced Study)

Abstract

The cation channel of sperm (CatSper) is essential for sperm motility and fertility1,2. CatSper comprises the pore-forming proteins CATSPER1–4 and multiple auxiliary subunits, including CATSPERβ, γ, δ, ε, ζ, and EFCAB91,3–9. Here we report the cryo-electron microscopy (cryo-EM) structure of the CatSper complex isolated from mouse sperm. In the extracellular view, CATSPER1–4 conform to the conventional domain-swapped voltage-gated ion channel fold10, following a counterclockwise arrangement. The auxiliary subunits CATSPERβ, γ, δ and ε—each of which contains a single transmembrane segment and a large extracellular domain—constitute a pavilion-like structure that stabilizes the entire complex through interactions with CATSPER4, 1, 3 and 2, respectively. Our EM map reveals several previously uncharacterized components, exemplified by the organic anion transporter SLCO6C1. We name this channel–transporter ultracomplex the CatSpermasome. The assembly and organization details of the CatSpermasome presented here lay the foundation for the development of CatSpermasome-related treatments for male infertility and non-hormonal contraceptives.

Suggested Citation

  • Shiyi Lin & Meng Ke & Yuqi Zhang & Zhen Yan & Jianping Wu, 2021. "Structure of a mammalian sperm cation channel complex," Nature, Nature, vol. 595(7869), pages 746-750, July.
  • Handle: RePEc:nat:nature:v:595:y:2021:i:7869:d:10.1038_s41586-021-03742-6
    DOI: 10.1038/s41586-021-03742-6
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    Cited by:

    1. Elena Grahn & Svenja V. Kaufmann & Malika Askarova & Momchil Ninov & Luisa M. Welp & Thomas K. Berger & Henning Urlaub & U.Benjamin Kaupp, 2023. "Control of intracellular pH and bicarbonate by CO2 diffusion into human sperm," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Yanhe Zhao & Huafeng Wang & Caroline Wiesehoefer & Naman B. Shah & Evan Reetz & Jae Yeon Hwang & Xiaofang Huang & Tse-en Wang & Polina V. Lishko & Karen M. Davies & Gunther Wennemuth & Daniela Nicastr, 2022. "3D structure and in situ arrangements of CatSper channel in the sperm flagellum," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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