Sperm needs a key to open the egg – 10/22/2024 – Science

The union of egg and sperm is crucial for all animals that reproduce sexually. But how this happened has remained a mystery to scientists.

one He studies Published last Thursday (17) in the magazine cell He explains that an interconnected package of three proteins is key to this process. This ray is shared by distantly related animals such as fish and mammals, and is likely present in humans as well.

Of almost all animals on Earth, the sperm cell makes its way to the egg cell membrane. Somehow, the two cells recognize each other and join together. Then, in the blink of an eye, the sperm’s head enters the egg, as if passing through a door. The fused cell becomes a zygote and is ready to develop into a new animal.

In previous research, scientists found four proteins in mammalian sperm that also appear in fish sperm and are essential for fertilization. However, no one knew if or how they could work as a team to insert the egg.

In the new study, molecular and developmental biologist Andrea Pauli of the Research Institute for Molecular Pathology in Vienna and collaborators from several institutions investigated how sperm proteins come together during fertilization.

The researchers relied on AlphaFold, developed by Google’s DeepMind, which was behind this year’s Nobel Prize in Chemistry.

Through the software, which uses artificial intelligence to predict protein shape, the team was able to compare the four sperm proteins shared between mammals and fish with a library of about 1,400 other proteins found on the cell surfaces of zebrafish testes, looking for possibilities for this to happen. Partners.

“We wanted to find something that we knew would be in the right place at the right time,” said Victoria Deneke, a postdoctoral researcher in Pauli’s lab.

Even for AlphaFold, this was a challenge. “It was running for two or three weeks,” Deneke said, monopolizing the campus’ computing resources.

“Other people at the institute weren’t so happy,” Pauley added.

AlphaFold predicted that two common native sperm proteins would bind to each other, along with a third, previously unknown protein, forming a triad.

Laboratory experiments confirmed the program’s hunch: male zebrafish lacking the newly discovered third protein were infertile, as were male mice. Their sperm swam normally, but were unable to fuse with the egg.

The scientists also found biochemical evidence that the three sperm proteins function as a single unit in both zebrafish and humans.

The same critical combination is likely present in many — or all — animals with spines, according to Pauli.

She described the set of sperm proteins as a kind of key that can be installed in the lock of the egg cell. In fish, this lock is a protein called a bouncer.

Previous research has also identified a lock molecule in mammalian eggs, which binds to one of the proteins in the three-protein group. But what is interesting is that the mammal lock is not the guard. It’s an unrelated protein called Juno.

This means that at some point in history, animals must have evolved different proteins to bind to the sperm protein package. This represents a mystery, according to Pauly. The lock had changed, but somehow “the key in the sperm remained the same,” she continued.

Earlier this year, a different research group independently used AlphaFold anticipation The same set of three proteins exists in mammals.

“The fact that two independent groups reached the same conclusions certainly increases our confidence in the results,” said Amber Kruchonas, a reproductive biologist from the University of Delaware, who was not involved in the new research.

“There is definitely more work to be done to unravel the secrets of fertilization,” the biologist said. For example, some sperm proteins are known to be shared between mammals and fish, but they are not part of this group. So what do they do?

“This is a fundamental question with very few molecular answers,” Pauli answered.