5jkd

From Proteopedia

Crystal structure of human IZUMO1-JUNO complex (crystal form 2)

PDB ID 5jkd

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Structural highlights

5jkd is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.9Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IZUM1_HUMAN Essential sperm cell-surface protein required for fertilization by acting as a ligand for IZUMO1R/JUNO receptor on egg. 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'.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Inoue N, Ikawa M, Isotani A, Okabe M. The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature. 2005 Mar 10;434(7030):234-8. PMID:15759005 doi:http://dx.doi.org/10.1038/nature03362
↑ 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