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Multi-state catch bond formed in the Izumo1:Juno complex that initiates human fertilization
Sean Boult1,2,3, Paulina Pacak3, Byeongseon Yang2
1Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
Nature Communications
|August 26, 2025
Summary
The human Izumo1:Juno complex forms a strong bond between sperm and egg cells, crucial for fertilization. Mechanical forces stabilize this complex, and a mutation linked to infertility weakens this crucial interaction.
Area of Science:
- Reproductive biology
- Biophysics
- Structural biology
Background:
- Sperm-egg cell adhesion is vital for mammalian fertilization.
- The Izumo1:Juno complex mediates this essential interaction.
- Limited understanding of the complex's mechanical regulation exists.
Purpose of the Study:
- To investigate the role of mechanical forces in the human Izumo1:Juno complex.
- To elucidate the mechanostability of sperm-egg binding.
- To explore the impact of infertility-associated mutations on complex stability.
Main Methods:
- Atomic force microscopy-based single-molecule force spectroscopy.
- All-atom steered molecular dynamic simulations.
- Analysis of force-dependent structural changes.
Main Results:
- The Izumo1:Juno complex exhibits multi-state catch bond behavior.
- The complex demonstrates remarkable mechanostability, resisting forces up to 600 pN.
- An infertility-associated mutant (JunoH177Q) shows impaired mechanostability.
- Force-induced structural reorganization reveals novel binding conformations.
Conclusions:
- Mechanical forces play a critical role in stabilizing human fertilization.
- The Izumo1:Juno complex possesses exceptional mechanostability, essential for reproductive success.
- Understanding these mechanical principles offers insights into infertility and potential therapeutic targets.
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