Genome complexity: how sperm enters egg (Introduction)

by David Turell , Friday, October 25, 2024, 15:49 (29 days ago) @ David Turell

Three proteins involved in the process:

https://www.sciencemagazinedigital.org/sciencemagazine/library/item/25_october_2024/422...

"Guided by its predictions, both have independently identified a complex of three proteins that sits on the head of a sperm and locks onto the surface of an egg cell during fertilization.

***

"In 2005, a team in Japan showed that deleting a particular gene in mice caused the animals to make healthy looking, motile sperm that nevertheless failed to fuse with egg cells. They named the gene Izumo1, after a Shinto shrine to marriage. Nearly a decade later, another group discovered a protein receptor on egg cells that bound to Izumo1, and named it Juno, after the Roman goddess of fertility. Others have found additional proteins: In 2020, for example, a team showed mice that had had their Spaca6 gene knocked out produced sperm with the same defects as rodents lacking Izumo1.

***

"In both teams’ studies, the AI program predicted the formation of a three-protein complex, or trimer, on sperm between Izumo1, Spaca6, and another known protein, Tmem81, which had not previously been associated with fertilization. In the eLife study, the team including Wright and led by structural biologist Luca Jovine at the Karolinska Institute analyzed mouse and human protein structures with the program and found the trimer could form a larger complex with Juno and another protein on egg cells called CD9.

"The other team, led by molecular biologist Andrea Pauli at the Research Institute of Molecular Pathology (IMP) at the Vienna Biocenter, went further and carried out experiments to see whether their AI-identified complex existed in the real world. They found that deleting the gene for Tmem81 in zebrafish and mice caused the same sperm defects as did deletions of Izumo1 or Spaca6, confirming this third protein was also critical for fertilization.

"The researchers also found that adding antibodies for Izumo1, Spaca6, or Tmem81 to samples of zebrafish sperm always pulled out all three proteins together, confirming they formed a trimer, as AI had predicted. “I think that was probably one of the happiest days in lab,” says Victoria Deneke, an IMP molecular biologist and co-author of the Cell paper. “It’s not a prediction … it’s actual experimental data.”

"Surprisingly, AlphaFold-Multimer also predicted—and experiments with zebrafish proteins subsequently supported— that different parts of this sperm trimer are responsible for binding to the distinctive receptors of mammalian versus zebrafish eggs. It’s remarkable that the sperm complex has stayed the same across vertebrate evolution whereas egg receptors have changed, Pauli says. The findings might reflect how eggs adapted to different environments—fish eggs are typically fertilized outside the animal, whereas mammalian eggs are fertilized within."

Comment: A complex of three proteins must be found by chance or the process is designed. Logically it is designed. especially considering the necesary eggv receptors.