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Title | ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat. |
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Journal, issue, pages | Cell, Vol. 187, Issue 6, Page 1440-1459.e24, Year 2024 |
Publish date | Mar 14, 2024 |
Authors | Shunsuke Nishio / Chihiro Emori / Benjamin Wiseman / Dirk Fahrenkamp / Elisa Dioguardi / Sara Zamora-Caballero / Marcel Bokhove / Ling Han / Alena Stsiapanava / Blanca Algarra / Yonggang Lu / Mayo Kodani / Rachel E Bainbridge / Kayla M Komondor / Anne E Carlson / Michael Landreh / Daniele de Sanctis / Shigeki Yasumasu / Masahito Ikawa / Luca Jovine / |
PubMed Abstract | Following the fertilization of an egg by a single sperm, the egg coat or zona pellucida (ZP) hardens and polyspermy is irreversibly blocked. These events are associated with the cleavage of the N- ...Following the fertilization of an egg by a single sperm, the egg coat or zona pellucida (ZP) hardens and polyspermy is irreversibly blocked. These events are associated with the cleavage of the N-terminal region (NTR) of glycoprotein ZP2, a major subunit of ZP filaments. ZP2 processing is thought to inactivate sperm binding to the ZP, but its molecular consequences and connection with ZP hardening are unknown. Biochemical and structural studies show that cleavage of ZP2 triggers its oligomerization. Moreover, the structure of a native vertebrate egg coat filament, combined with AlphaFold predictions of human ZP polymers, reveals that two protofilaments consisting of type I (ZP3) and type II (ZP1/ZP2/ZP4) components interlock into a left-handed double helix from which the NTRs of type II subunits protrude. Together, these data suggest that oligomerization of cleaved ZP2 NTRs extensively cross-links ZP filaments, rigidifying the egg coat and making it physically impenetrable to sperm. |
External links | Cell / PubMed:38490181 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.9 - 4.6 Å |
Structure data | EMDB-19276: Cryo-EM of tetrameric collagenase-cleaved Xenopus ZP2-N2N3 (cleaved xZP2-N2N3) (C1) EMDB-19277: Cryo-EM of tetrameric collagenase-cleaved Xenopus ZP2-N2N3 (cleaved xZP2-N2N3) (C2) PDB-8bqu: PDB-8rke: PDB-8rkf: PDB-8rkg: PDB-8rkh: PDB-8rki: |
Chemicals | ChemComp-NAG: ChemComp-HOH: ChemComp-NO3: ChemComp-BCN: ChemComp-YB: |
Source |
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Keywords | STRUCTURAL PROTEIN / Cell adhesion / fertilization / egg-sperm interaction / gamete recognition / sperm receptor / extracellular matrix / egg coat / zona pellucida / vitelline envelope / fish chorion / glycoprotein / N-glycan / ZP module / ZP-N domain / ZP_C domain / trefoil domain / medaka / Japanese rice fish / block to polyspermy / post-fertilization cleavage / ovastacin / AlphaFold / ZP-C domain |