For the study, the researchers analysed the X-ray crystal structure of IZUMO1 as it came in contact with OBF13. The researchers found that OBF13 attaches itself to sperm in such a way that it reconfigures the way sperm come into contact with an egg. The analysis also identified a high-affinity (tightly bonding) variant of OBF13 that potently blocks egg-sperm fertilisation.

In addition, the researchers identified key amino acid sites on JUNO that define its ability to bind with IZUMO1. When accessed, these sites are able to bind sperm and egg for fertilisation despite interference from OBF13 or its variant.

“In this work, we are reporting the first anti-sperm antibody-antigen complex structure,” Tang said. “We provide high-resolution information that will open avenues for discovering IZUMO1 regulators, guide antibody and small-molecule inhibitor design, and support drug screening for contraceptive development.”

The study’s first author is Yonggang Lu of Osaka University. Masahito Ikawa, also from Osaka University, is the study’s co-author.

The work was supported, in part, by the National Institutes of Health, a David Sokal Innovation Award of Male Contraception Initiative, the Japan Society for the Promotion of Science, the Japan Agency for Medical Research and Development, and a grant from the Takeda Science Foundation. The researchers also made use of facilities at the SLAC National Accelerator Laboratory in California, which is supported by the U.S. Department of Energy’s Office of Science.