ZP2 cleavage blocks polyspermy by modulating the architecture of the egg coat

• Published in: Cell Vol. 187; no. 6; pp. 1440 - 1459.e24
• Main Authors: Nishio, Shunsuke, Emori, Chihiro, Wiseman, Benjamin, Fahrenkamp, Dirk, Dioguardi, Elisa, Zamora-Caballero, Sara, Bokhove, Marcel, Han, Ling, Stsiapanava, Alena, Algarra, Blanca, Lu, Yonggang, Kodani, Mayo, Bainbridge, Rachel E., Komondor, Kayla M., Carlson, Anne E., Landreh, Michael, de Sanctis, Daniele, Yasumasu, Shigeki, Ikawa, Masahito, Jovine, Luca
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.03.2024
• Subjects: block to polyspermy; egg coat hardening; egg-sperm interaction; fertilization; integrative structural biology; Medicin och hälsovetenskap; zona pellucida; ZP protein filament; ZP1; ZP2 cleavage; ZP3; block to polyspermy; fertilization; zona pellucida; egg-sperm interaction; ZP protein filament; ZP1; integrative structural biology; egg coat hardening; ZP2 cleavage; ZP3
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2024.02.013

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. [Display omitted] •Post-fertilization cleavage of zona pellucida (ZP) subunit ZP2 makes it oligomerize•Premature ZP2 oligomerization causes infertility by impairing sperm penetration of ZP•A native egg coat fragment structure sheds light on heteromeric ZP filament assembly•Cleaved ZP2 cross-links ZP filaments to harden the egg coat and prevent polyspermy Post-fertilization cleavage of the egg zona pellucida (ZP) subunit ZP2 triggers its oligomerization, which in turn cross-links the filaments that make up the ZP. By tightening its mesh, this hardens the egg coat matrix and hinders the penetration of further sperm, thereby ensuring a permanent block to polyspermy.