The highly conserved nature of the proteins that allow sperm and egg binding has been identified using artificial intelligence (AI).
In sexually reproducing organisms the first step of fertilisation is for the sperm and egg to bind. While previous research has identified two proteins crucial for fertilisation: JUNO, which appears on the egg cell, and IZUMO1, which is on the sperm cell surface, researchers were unclear on whether other proteins were involved and how they all interacted with each other (see BioNews 1226, 1171 and 751). Now researchers have identified three proteins on the sperm that join together to form a structure which 'unlocks' the egg, and found they are highly conserved across vertebrates.
Dr Andrea Pauli, co-author of the study and senior group leader at the Research Institute of Molecular Pathology in Vienna, Austria, said that this newly discovered mechanism is 'really fundamental across all vertebrates as far as we can tell.'
To carry out their research the scientists used AlphaFold, an AI tool which predicts the shape of proteins and whose creators at Google DeepMind were recently awarded the Nobel Prize for Chemistry (see BioNews 1260). The researchers focused on four proteins already known to be involved in fertilisation in both mammals and fish, and used AlphaFold to try to identify potential new proteins that might interact with them.
AlphaFold successfully identified a new protein on sperm not previously associated with fertility called Tmem81 and predicted that it would bind with two of the original fertilisation proteins. In both fish and mammals, these three proteins assemble into bundles which allows binding of the sperm with the egg.
To confirm their findings, the scientists engineered zebrafish and mice that lacked the newly discovered fertilisation protein. They discovered that the absence of this protein led to infertility, as the sperm was unable to bind with the egg.
The researchers hope that this work will be used to understand infertility better, or to contribute to the development of new birth control methods.
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