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

Sean Boult, Paulina Pacak, Byeongseon Yang, Haipei Liu, Viola Vogel () and Michael A. Nash ()
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Sean Boult: ETH Zürich
Paulina Pacak: ETH Zürich
Byeongseon Yang: University of Basel
Haipei Liu: University of Basel
Viola Vogel: ETH Zürich
Michael A. Nash: ETH Zürich

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62427-0

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