Structural highlights
Function
JUNO_HUMAN Receptor for IZUMO1 present at the cell surface of oocytes (oolemma), which is essential for species-specific gamete recognition and fertilization. The IZUMO1:IZUMO1R/JUNO interaction is a necessary adhesion event between sperm and egg that is required for fertilization but is not sufficient for cell fusion. The ligand-receptor interaction probably does not act as a membrane 'fusogen'. Does not bind folate.[UniProtKB:Q9EQF4]
Publication Abstract from PubMed
Fertilization is a fundamental process in sexual reproduction, creating a new individual through the combination of male and female gametes. The IZUMO1 sperm membrane protein and its counterpart oocyte receptor JUNO have been identified as essential factors for sperm-oocyte interaction and fusion. However, the mechanism underlying their specific recognition remains poorly defined. Here, we show the crystal structures of human IZUMO1, JUNO and the IZUMO1-JUNO complex, establishing the structural basis for the IZUMO1-JUNO-mediated sperm-oocyte interaction. IZUMO1 exhibits an elongated rod-shaped structure comprised of a helical bundle IZUMO domain and an immunoglobulin-like domain that are each firmly anchored to an intervening beta-hairpin region through conserved disulfide bonds. The central beta-hairpin region of IZUMO1 provides the main platform for JUNO binding, while the surface located behind the putative JUNO ligand binding pocket is involved in IZUMO1 binding. Structure-based mutagenesis analysis confirms the biological importance of the IZUMO1-JUNO interaction. This structure provides a major step towards elucidating an essential phase of fertilization and it will contribute to the development of new therapeutic interventions for fertility, such as contraceptive agents.
Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization.,Ohto U, Ishida H, Krayukhina E, Uchiyama S, Inoue N, Shimizu T Nature. 2016 Jun 15;534(7608):566-9. doi: 10.1038/nature18596. PMID:27309808[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ohto U, Ishida H, Krayukhina E, Uchiyama S, Inoue N, Shimizu T. Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization. Nature. 2016 Jun 15;534(7608):566-9. doi: 10.1038/nature18596. PMID:27309808 doi:http://dx.doi.org/10.1038/nature18596
