{"doi":"10.1101/2024.08.13.607777","title":"Torsional Twist of the SARS-CoV and SARS-CoV-2 SUD-N and SUD-M domains","abstract":"Coronavirus non-structural protein 3 (nsp3) forms hexameric crowns of pores in the double membrane vacuole that houses the replication-transcription complex. Nsp3 in SARS-like viruses has three unique domains absent in other coronavirus nsp3 proteins. Two of these, SUD-N (Macrodomain 2) and SUD-M (Macrodomain 3), form two lobes connected by a peptide linker and an interdomain disulfide bridge. We resolve the first complete x-ray structure of SARS-CoV SUD-N/M as well as a mutant variant of SARS-CoV-2 SUD-N/M modified to restore cysteines for interdomain disulfide bond naturally lost by evolution. Comparative analysis of all structures revealed SUD-N and SUD-M are not rigidly associated, but rather, have significant rotational flexibility. Phylogenetic analysis supports that the disulfide bond cysteines are also absent in pangolin-SARS and closely related viruses, consistent with pangolins being the presumed intermediate host in the emergence of SARS-CoV-2. The absence of these cysteines does not impact viral replication or protein translation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":488831,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9417,"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":530033,"name":"G. Minasov","orcid":"0000-0001-5460-3462","position":1,"is_corresponding":false},{"id":563091,"name":"J.S. Brunzelle","orcid":"0000-0001-9197-0018","position":2,"is_corresponding":false},{"id":385627,"name":"Taha Y. Taha","orcid":"0000-0002-7344-7490","position":3,"is_corresponding":false},{"id":1299108,"name":"Sofia Lemak","orcid":null,"position":4,"is_corresponding":false},{"id":351235,"name":"Shaohui Yin","orcid":"0000-0002-9358-6113","position":5,"is_corresponding":false},{"id":530036,"name":"L. Shuvalova","orcid":"0000-0003-1702-6998","position":6,"is_corresponding":false},{"id":1333387,"name":"Julia Rosecrans","orcid":"0009-0000-3111-5933","position":7,"is_corresponding":false},{"id":293149,"name":"Kanika Khanna","orcid":"0000-0001-7150-0350","position":8,"is_corresponding":false},{"id":146865,"name":"H Steven Seifert","orcid":"0000-0001-8651-0375","position":9,"is_corresponding":false},{"id":303941,"name":"Alexei Savchenko","orcid":"0000-0002-5256-9237","position":10,"is_corresponding":false},{"id":344681,"name":"P.J. Stogios","orcid":"0000-0001-8663-1425","position":11,"is_corresponding":false},{"id":103701,"name":"Mélanie Ott","orcid":"0000-0002-5697-1274","position":12,"is_corresponding":false},{"id":36778,"name":"Karla J. F. Satchell","orcid":"0000-0003-3274-7611","position":13,"is_corresponding":false},{"id":493829,"name":"Mónica Rosas‐Lemus","orcid":"0000-0002-6243-0271","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:08:19.655720Z","pmid":"39185168","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":[]}