{"doi":"10.1038/s42003-024-05768-8","title":"A conformational selection mechanism of flavivirus NS5 for species-specific STAT2 inhibition","abstract":"Flaviviruses, including Zika virus (ZIKV) and Dengue virus (DENV), rely on their non-structural protein 5 (NS5) for both replication of viral genome and suppression of host IFN signaling. DENV and ZIKV NS5s were shown to facilitate proteosome-mediated protein degradation of human STAT2 (hSTAT2). However, how flavivirus NS5s have evolved for species-specific IFN-suppression remains unclear. Here we report structure-function characterization of the DENV serotype 2 (DENV2) NS5-hSTAT2 complex. The MTase and RdRP domains of DENV2 NS5 form an extended conformation to interact with the coiled-coil and N-terminal domains of hSTAT2, thereby promoting hSTAT2 degradation in cells. Disruption of the extended conformation of DENV2/ZIKV NS5, but not the alternative compact state, impaired their hSTAT2 binding. Our comparative structural analysis of flavivirus NS5s further reveals a conserved protein-interaction platform with subtle amino-acid variations likely underpinning diverse IFN-suppression mechanisms. Together, this study uncovers a conformational selection mechanism underlying species-specific hSTAT2 inhibition by flavivirus NS5.","journal":"Communications Biology","year":2024,"id":424450,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":1220910,"name":"Wangyuan Yao","orcid":"0000-0001-9428-9973","position":1,"is_corresponding":false},{"id":247175,"name":"Jiuwei Lu","orcid":"0000-0002-6478-4081","position":2,"is_corresponding":false},{"id":1054129,"name":"Jianbin Chen","orcid":"0009-0001-6188-4853","position":3,"is_corresponding":false},{"id":547194,"name":"Juliet Morrison","orcid":"0000-0001-7387-6351","position":4,"is_corresponding":false},{"id":305642,"name":"Rong Hai","orcid":"0000-0002-0577-4676","position":5,"is_corresponding":false},{"id":247180,"name":"Jikui Song","orcid":"0000-0002-4958-1032","position":6,"is_corresponding":false},{"id":486736,"name":"Mahamaya Biswal","orcid":"0000-0002-8995-2635","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:58:07.191194Z","pmid":"38195857","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":[]}