{"doi":"10.1101/2023.06.21.544075","title":"Architecture of the vertebrate egg coat and structural basis of the ZP2 block to polyspermy","abstract":"SUMMARY Post-fertilization cleavage of glycoprotein ZP2, a major subunit of egg zona pellucida (ZP) filaments, is crucial for mammalian reproduction by irreversibly blocking polyspermy. ZP2 processing is thought to inactivate a sperm-binding activity located upstream of the protein’s cleavage site; however, its molecular consequences and connection with ZP hardening are unknown. Here we report X-ray crystallographic, cryo-EM and biochemical studies showing that cleavage of ZP2 triggers its oligomerization. Deletion of the ZP-N1 domain that precedes the cleavage site of mouse ZP2 allows it to homodimerize even without processing, and animals homozygous for this variant are subfertile by having a semi-hardened ZP that allows sperm attachment but hinders penetration. Combined with the structure of a native egg coat filament, which reveals the molecular basis of heteromeric ZP subunit interaction, this suggests that oligomerization of cleaved ZP2 cross-links the ZP, rigidifying it and making it physically impenetrable to sperm.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":399903,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9468,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":401645,"name":"Chihiro Emori","orcid":"0000-0001-8040-2517","position":1,"is_corresponding":false},{"id":1176233,"name":"Benjamin Wiseman","orcid":"0000-0002-2994-5839","position":2,"is_corresponding":false},{"id":1176234,"name":"Dirk Fahrenkamp","orcid":"0000-0003-1149-5910","position":3,"is_corresponding":false},{"id":1176235,"name":"Elisa Dioguardi","orcid":"0000-0002-8734-8178","position":4,"is_corresponding":false},{"id":1176236,"name":"Sara Zamora‐Caballero","orcid":"0000-0003-4717-8845","position":5,"is_corresponding":false},{"id":1176237,"name":"Marcel Bokhove","orcid":"0000-0001-7241-5967","position":6,"is_corresponding":false},{"id":481287,"name":"Ling Han","orcid":"0000-0001-9310-4789","position":7,"is_corresponding":false},{"id":1176238,"name":"Alena Stsiapanava","orcid":"0000-0001-6560-011X","position":8,"is_corresponding":false},{"id":989108,"name":"Yonggang Lu","orcid":"0000-0003-0198-8906","position":9,"is_corresponding":false},{"id":1055220,"name":"Mayo Kodani","orcid":"0000-0002-3178-5985","position":10,"is_corresponding":false},{"id":380636,"name":"Rachel E. Bainbridge","orcid":"0000-0002-6014-2030","position":11,"is_corresponding":false},{"id":963347,"name":"Kayla M. Komondor","orcid":"0000-0002-2452-7443","position":12,"is_corresponding":false},{"id":380649,"name":"Anne E. Carlson","orcid":"0000-0003-2724-1325","position":13,"is_corresponding":false},{"id":314460,"name":"Michael Landreh","orcid":"0000-0002-7958-4074","position":14,"is_corresponding":false},{"id":1176239,"name":"Daniele de Sanctis","orcid":"0000-0003-0391-8290","position":15,"is_corresponding":false},{"id":1176240,"name":"Shigeki Yasumasu","orcid":"0000-0003-4295-477X","position":16,"is_corresponding":false},{"id":275906,"name":"Masahito Ikawa","orcid":"0000-0001-9859-6217","position":17,"is_corresponding":false},{"id":481286,"name":"Luca Jovine","orcid":"0000-0002-2679-6946","position":18,"is_corresponding":false},{"id":1176232,"name":"Shunsuke Nishio","orcid":"0000-0003-3420-2578","position":0,"is_corresponding":true}],"reference_count":151,"raw_metadata":null,"created_at":"2026-07-19T01:20:00.023537Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}