{"doi":"10.1016/j.celrep.2022.110786","title":"Inter-domain communication in SARS-CoV-2 spike proteins controls protease-triggered cell entry","abstract":"SARS-CoV-2 continues to evolve into variants of concern (VOC), with greatest variability in the multidomain, entry-facilitating spike proteins. To recognize the significance of adaptive spike protein changes, we compare variant SARS-CoV-2 virus particles in several assays reflecting authentic virus-cell entry. Virus particles with adaptive changes in spike amino-terminal domains (NTDs) are hypersensitive to proteolytic activation of membrane fusion, an essential step in virus-cell entry. Proteolysis is within fusion domains (FDs), at sites over 10 nm from the VOC-specific NTD changes, indicating allosteric inter-domain control of fusion activation. In addition, NTD-specific antibodies block FD cleavage, membrane fusion, and virus-cell entry, suggesting restriction of inter-domain communication as a neutralization mechanism. Finally, using structure-guided mutagenesis, we identify an inter-monomer β sheet structure that facilitates NTD-to-FD transmissions and subsequent fusion activation. This NTD-to-FD axis that sensitizes viruses to infection and to NTD-specific antibody neutralization provides new context for understanding selective forces driving SARS-CoV-2 evolution.","journal":"Cell Reports","year":2022,"id":237633,"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":59,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9559,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":477099,"name":"Pengfei Li","orcid":"0000-0001-6436-4573","position":1,"is_corresponding":false},{"id":551886,"name":"Laura Cooper","orcid":"0000-0002-6322-1260","position":2,"is_corresponding":false},{"id":860411,"name":"Sebastian Schulz","orcid":"0000-0001-6554-3346","position":3,"is_corresponding":false},{"id":860412,"name":"Hans‐Martin Jäck","orcid":"0000-0002-6332-8463","position":4,"is_corresponding":false},{"id":361641,"name":"Lijun Rong","orcid":"0000-0003-3938-0445","position":5,"is_corresponding":false},{"id":77538,"name":"Stanley Perlman","orcid":"0000-0003-4213-2354","position":6,"is_corresponding":false},{"id":241084,"name":"Tom Gallagher","orcid":"0000-0002-8601-5961","position":7,"is_corresponding":false},{"id":274112,"name":"Enya Qing","orcid":"0000-0002-7455-3463","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T00:22:21.693802Z","pmid":"35477024","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":[]}