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Multi-state catch bond formed in the Izumo1:Juno complex that initiates human fertilization

Author

Listed:
  • Sean Boult

    (ETH Zürich
    University of Basel
    ETH Zürich)

  • Paulina Pacak

    (ETH Zürich)

  • Byeongseon Yang

    (University of Basel)

  • Haipei Liu

    (University of Basel)

  • Viola Vogel

    (ETH Zürich
    Molecular Systems Engineering)

  • Michael A. Nash

    (ETH Zürich
    University of Basel
    Molecular Systems Engineering
    Swiss Nanoscience Institute)

Abstract

Izumo1:Juno-mediated adhesion between sperm and egg cells is essential for mammalian sexual reproduction. However, conventional biophysical and structural approaches have provided only limited functional insights. Using atomic force microscopy-based single-molecule force spectroscopy and all-atom steered molecular dynamic simulations, we explore the role of mechanical forces in regulating the human Izumo1:Juno complex. Our findings reveal a multi-state catch bond capable of withstanding forces up to 600 pN– mechanostability rarely observed among eukaryotic protein complexes. We find that this enhanced mechanostability is impaired in the infertility-associated mutant, JunoH177Q. Detailed steered molecular dynamics simulations show how force-dependent structural reorganization of the Izumo1:Juno complex engages previously undiscovered binding conformations to achieve this state of high mechanostability. Overall, this study significantly enhances our understanding of the mechanical underpinnings that regulate human fertilization.

Suggested Citation

  • Sean Boult & Paulina Pacak & Byeongseon Yang & Haipei Liu & Viola Vogel & Michael A. Nash, 2025. "Multi-state catch bond formed in the Izumo1:Juno complex that initiates human fertilization," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62427-0
    DOI: 10.1038/s41467-025-62427-0
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    References listed on IDEAS

    as
    1. Enrica Bianchi & Brendan Doe & David Goulding & Gavin J. Wright, 2014. "Juno is the egg Izumo receptor and is essential for mammalian fertilization," Nature, Nature, vol. 508(7497), pages 483-487, April.
    2. Halil Aydin & Azmiri Sultana & Sheng Li & Annoj Thavalingam & Jeffrey E. Lee, 2016. "Molecular architecture of the human sperm IZUMO1 and egg JUNO fertilization complex," Nature, Nature, vol. 534(7608), pages 562-565, June.
    3. Naokazu Inoue & Yoshihisa Hagihara & Danelle Wright & Takahisa Suzuki & Ikuo Wada, 2015. "Oocyte-triggered dimerization of sperm IZUMO1 promotes sperm–egg fusion in mice," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
    4. Naokazu Inoue & Masahito Ikawa & Ayako Isotani & Masaru Okabe, 2005. "The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs," Nature, Nature, vol. 434(7030), pages 234-238, March.
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