| First Author | Ohto U | Year | 2016 |
| Journal | Nature | Volume | 534 |
| Issue | 7608 | Pages | 566-9 |
| PubMed ID | 27309808 | Mgi Jnum | J:235303 |
| Mgi Id | MGI:5796060 | Doi | 10.1038/nature18596 |
| Citation | Ohto U, et al. (2016) Structure of IZUMO1-JUNO reveals sperm-oocyte recognition during mammalian fertilization. Nature 534(7608):566-9 |
| abstractText | 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. |
