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

Sara Zamora-Caballero, Shigeki Yasumasu, Anne E Carlson, Kayla M Komondor, Rachel E Bainbridge, Mayo Kodani, Yonggang Lu, Blanca Algarra, Alena Stsiapanava, Marcel Bokhove, Ling Han, Elisa Dioguardi, Dirk Fahrenkamp, Benjamin Wiseman, Chihiro Emori, Shunsuke Nishio, Michael Landreh, Masahito Ikawa, Daniele de Sanctis, Luca Jovine

Journal: Cell 2024;187(6):1440-1459.e24

PMID: 38490181

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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-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.

Address: Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.; Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.; Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan.; Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Cell and Molecular Biology, Uppsala University, 75124 Uppsala, Sweden.; ESRF - The European Synchrotron, Grenoble, France.; Department of Materials and Life Sciences, Faculty of Science and Technology, Sophia University, Tokyo, Japan.; Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan; Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan; Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan; Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Osaka, Japan.; Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. Electronic address: [email protected].

DOI: 10.1016/j.cell.2024.02.013

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MeSH Terms: Humans, Male, Semen, Spermatozoa, Zona Pellucida, Zona Pellucida Glycoproteins, Ovum, Female