{"doi":"10.1101/2025.10.16.682669","title":"An unconventional HxD motif orchestrates coatomer-dependent coronavirus morphogenesis","abstract":"Assembly of infectious coronaviruses requires spike (S) protein trafficking by host coatomer, typically via a dibasic signal in the S cytoplasmic tail. However, the human embecoviruses HKU1 and OC43, as well as the model virus MHV, lack this motif. Here we identify a conserved His-x-Asp (HxD) sequence that functions as an unconventional coatomer-binding signal. Structural and biochemical analyses show that the MHV HxD motif engages coatomer subunits through distinct conformations, while cellular imaging demonstrates its role in directing S to assembly sites with the viral M-protein. Disruption of HxD-coatomer interactions impairs S incorporation and provokes compensatory viral adaptations, including emergence of a canonical dibasic motif or mutations in M-protein. Electron microscopy further reveals profound alterations in virion surface architecture. These findings uncover HxD as a previously unrecognized coatomer-targeting motif, highlighting an unexpected flexibility in coronavirus assembly pathways and broadening understanding of the cellular machinery that shapes coronavirus morphogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":578467,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1156730,"name":"Anil Kumar Shakya","orcid":"0000-0003-0637-652X","position":1,"is_corresponding":false},{"id":570356,"name":"Suruchi Singh","orcid":"0000-0002-4306-9345","position":2,"is_corresponding":false},{"id":226463,"name":"Fiona L. Kearns","orcid":"0000-0002-5469-9035","position":3,"is_corresponding":false},{"id":1488426,"name":"Kezia Jemison","orcid":null,"position":4,"is_corresponding":false},{"id":266717,"name":"Satchal K. Erramilli","orcid":"0000-0001-8694-7681","position":5,"is_corresponding":false},{"id":817864,"name":"Debajit Dey","orcid":"0000-0001-8289-7904","position":6,"is_corresponding":false},{"id":274112,"name":"Enya Qing","orcid":"0000-0002-7455-3463","position":7,"is_corresponding":false},{"id":691055,"name":"Benjamin C. Jennings","orcid":"0000-0002-7255-2715","position":8,"is_corresponding":false},{"id":691057,"name":"Balraj Doray","orcid":"0000-0003-3347-5013","position":9,"is_corresponding":false},{"id":260362,"name":"Anthony A. Kossiakoff","orcid":"0000-0003-3174-9359","position":10,"is_corresponding":false},{"id":71085,"name":"Rommie E. Amaro","orcid":"0000-0002-9275-9553","position":11,"is_corresponding":false},{"id":327015,"name":"Thomas Klose","orcid":"0000-0002-2150-9792","position":12,"is_corresponding":false},{"id":241084,"name":"Tom Gallagher","orcid":"0000-0002-8601-5961","position":13,"is_corresponding":false},{"id":463836,"name":"S. Saif Hasan","orcid":"0000-0002-0759-7511","position":14,"is_corresponding":false},{"id":1473066,"name":"Surovi Binte Sharmin Mohona","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T02:58:20.638044Z","pmid":"41279991","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":[]}