{"doi":"10.1016/j.cell.2024.06.006","title":"Human coronavirus HKU1 recognition of the TMPRSS2 host receptor","abstract":"The human coronavirus HKU1 spike (S) glycoprotein engages host cell surface sialoglycans and transmembrane protease serine 2 (TMPRSS2) to initiate infection. The molecular basis of HKU1 binding to TMPRSS2 and determinants of host receptor tropism remain elusive. We designed an active human TMPRSS2 construct enabling high-yield recombinant production in human cells of this key therapeutic target. We determined a cryo-electron microscopy structure of the HKU1 RBD bound to human TMPRSS2, providing a blueprint of the interactions supporting viral entry and explaining the specificity for TMPRSS2 among orthologous proteases. We identified TMPRSS2 orthologs from five mammalian orders promoting HKU1 S-mediated entry into cells along with key residues governing host receptor usage. Our data show that the TMPRSS2 binding motif is a site of vulnerability to neutralizing antibodies and suggest that HKU1 uses S conformational masking and glycan shielding to balance immune evasion and receptor engagement.","journal":"Cell","year":2024,"id":419139,"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":43,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":97052,"name":"Young‐Jun Park","orcid":"0000-0003-2901-6949","position":1,"is_corresponding":false},{"id":828534,"name":"Cameron Stewart","orcid":"0000-0002-2786-6256","position":2,"is_corresponding":false},{"id":614555,"name":"Kaitlin R. Sprouse","orcid":"0000-0003-0007-2226","position":3,"is_corresponding":false},{"id":294604,"name":"Amin Addetia","orcid":"0000-0001-6703-3841","position":4,"is_corresponding":false},{"id":732002,"name":"Jack Brown","orcid":null,"position":5,"is_corresponding":false},{"id":97048,"name":"M. Alejandra Tortorici","orcid":"0000-0002-2260-2577","position":6,"is_corresponding":false},{"id":1209100,"name":"C Gibson","orcid":null,"position":7,"is_corresponding":false},{"id":250374,"name":"Emily Wong","orcid":"0000-0003-4755-5380","position":8,"is_corresponding":false},{"id":1208425,"name":"Margareta Ieven","orcid":"0000-0002-1608-0645","position":9,"is_corresponding":false},{"id":29722,"name":"Amalio Telenti","orcid":"0000-0001-6290-7677","position":10,"is_corresponding":false},{"id":97051,"name":"David Veesler","orcid":"0000-0002-6019-8675","position":11,"is_corresponding":false},{"id":225081,"name":"Matthew McCallum","orcid":"0000-0001-8398-8330","position":0,"is_corresponding":true}],"reference_count":118,"raw_metadata":null,"created_at":"2026-07-19T01:57:14.586331Z","pmid":"38964328","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":[]}