Simulations reveal what happens when a sperm accepts an egg: ScienceAlert
The moment when the gliding sperm propels itself head first into the gelatinous egg is a moment of sudden change. Within seconds to minutes, chemical changes occur in the egg’s membrane and outer covering to prevent any other sperm from attaching to and entering the egg.
A series of reactions also occur when the sperm and egg recognize each other, chemically, and then begin to fuse their membranes together. But despite the importance of these precise molecular events, their details have not been fully resolved.
A new study conducted by researchers at ETH Zurich and Ludwig Maximilian University of Munich in Switzerland has revealed the intricacies of a special protein complex known for its crucial role in the fertilization process.
“It was hypothesized that combining the two proteins (JUNO and IZUMO1) in a complex initiates the process of recognition and adhesion between germ cells, thus enabling their fusion,” explains Polina Bakak, a bioinformatician at ETH Zurich and first author of the research book. Stady.
This interaction between JUNO – located on the outer membrane of the female egg cell – and IZUMO1, located on the surface of the male sperm cell, is the first known physical link between two newly merging sex cells.
However, efforts to develop small molecule inhibitors of the JUNO-IZUMO1 conjugate, as a potential means of contraception, have not gone far enough, so researchers suspect that there may be more to their molecular interactions than we know.
Techniques commonly used to learn the structure of individual proteins and protein complexes, such as cryo-electron microscopy and protein crystallography, also involve snap-freezing or crystallizing proteins, meaning they only produce a static image of these protein structures and can… t capture their dynamic interactions.
But inside cells, proteins are constantly being synthesized and shaped, floating in the watery mixture of the cytoplasm, attaching to and dissociating from their partners, and being recycled.
So, Bakak and his colleagues used a Swiss supercomputer to simulate the interactions between JUNO and IZUMO1 in water, thus more closely resembling their natural conformations in cells.
Each simulation lasted only 200 nanoseconds each, but showed that the JUNO-IZUMO1 complex was initially stabilized by a set of short-lived, weak noncovalent interactions between protein molecules.
These communications took less than 50 nanoseconds each, and the researchers suggest that understanding what happens when they are interrupted, either by other molecules or mutations, could provide insight into contraception and infertility.
Next, Bakak and his colleagues simulated how the long-term bonds holding the JUNO-IZUMO1 complex together could be destabilized by zinc ions.
Minutes after sperm and egg unite, the fertilized egg releases a flood of charged zinc atoms that are thought to prevent other sperm from entering the egg by hardening its outer shell.
Simulations showed that the presence of zinc ions caused IZUMO1 to bend into a bouncy conformation, so it could no longer bind strongly to JUNO. This suggests that the egg’s release of zinc could also hinder the attachment of approaching sperm.
While this is just a computer simulation based on protein sequences and shapes, the results provide new insight into the first moments of fertilization.
“We can only detect something like this with the help of simulations,” says Viola Vogel, a biophysicist at ETH Zurich and lead researcher.
“The conclusions we draw from them would not be possible on the basis of fixed crystal structures of proteins.”
The study was published in Scientific reports.