OBF13 (Okabe, Butsu-Metsu, Friday the 13th), is a mouse anti-sperm antibody first isolated in the 1980s by Professor Emeritus Masaru Okabe (RIMD, Osaka University). It blocks in vitro fertilization in mice and recognizes sperm IZUMO1, a protein essential for mammalian sperm–egg fusion through its interaction with egg JUNO. However, the mechanism by which OBF13 inhibits fertilization had remained unclear for the past 40 years.
This new study, led by Yonggang Lu (WPI-PRIMe, Osaka University) and Shaogeng Tang (MB&B, Yale University), unlocks the structural and molecular basis of OBF13-mediated allosteric inhibition of IZUMO1–JUNO interaction. OBF13 binds to the four-helix bundle of IZUMO1, preventing the conformational change in its ectodomain necessary for JUNO binding. As a result, sperm exposed to OBF13 lose their ability to attach to the egg plasma membrane, ultimately leading to fertilization failure.
These findings provide new insights into the diagnosis and treatment of immuno-infertility, and open avenues for the development of immunocontraceptives.