Beginning of life: molecular "lock-and-key" of fertilisation found

Genetic studies have identified many proteins that contribute to the first contact between egg and sperm. However, no direct evidence has yet demonstrated how these factors bind or form complexes to carry out their function as a “lock-and-key” mechanism. Now, Andrea Pauli’s lab at the Research Institute of Molecular Pathology (IMP) and collaborators combined Artificial Intelligence-driven structural predictions with direct experimental evidence to reveal the formation of a fertilization complex. Their findings, drawn from studies in zebrafish, mice, and human cells, are published in the journal Cell.

A fluorescence microscopy image of a mouse egg, in red and green, and sperm, in blue. Credit: Yonggang Lu/Osaka University

Over the past 20 years, many proteins have been identified as essential for the interaction between mammalian sperm and egg. However, only two—Izumo1, found on the surface of the sperm, and Juno, located on the egg’s membrane—have been confirmed to directly bind to each other to facilitate fertilization.

Using the latest advancements of the Artificial Intelligence (AI) tool AlphaFold, Andrea Pauli’s lab at the IMP and international collaborators now identified a new protein complex that facilitates the first molecular connection between sperm and egg and demonstrated its function in living organisms. The findings, published in the journal Cell, reveal that a fundamental lock-and-key mechanism crucial for fertilization is shared across vertebrates.

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