{"doi":"10.1016/j.jbc.2023.104777","title":"Structural basis of DNA binding by the WhiB-like transcription factor WhiB3 in Mycobacterium tuberculosis","abstract":"Mycobacterium tuberculosis ( Mtb ) WhiB3 is an iron–sulfur cluster-containing transcription factor belonging to a subclass of the WhiB-Like (Wbl) family that is widely distributed in the phylum Actinobacteria. WhiB3 plays a crucial role in the survival and pathogenesis of Mtb . It binds to the conserved region 4 of the principal sigma factor (σ A 4 ) in the RNA polymerase holoenzyme to regulate gene expression like other known Wbl proteins in Mtb . However, the structural basis of how WhiB3 coordinates with σ A 4 to bind DNA and regulate transcription is unclear. Here we determined crystal structures of the WhiB3:σ A 4 complex without and with DNA at 1.5 Å and 2.45 Å, respectively, to elucidate how WhiB3 interacts with DNA to regulate gene expression. These structures reveal that the WhiB3:σ A 4 complex shares a molecular interface similar to other structurally characterized Wbl proteins and also possesses a subclass-specific Arg-rich DNA-binding motif. We demonstrate that this newly defined Arg-rich motif is required for WhiB3 binding to DNA in vitro and transcriptional regulation in Mycobacterium smegmatis . Together, our study provides empirical evidence of how WhiB3 regulates gene expression in Mtb by partnering with σ A 4 and engaging with DNA via the subclass-specific structural motif, distinct from the modes of DNA interaction by WhiB1 and WhiB7.","journal":"Journal of Biological Chemistry","year":2023,"id":362116,"datarank":0.32958368660043297,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.0,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":744203,"name":"Magdaléna Horová","orcid":null,"position":1,"is_corresponding":false},{"id":1115756,"name":"Vimmy Khetrapal","orcid":null,"position":2,"is_corresponding":false},{"id":743529,"name":"Shanren Li","orcid":"0000-0001-9302-7998","position":3,"is_corresponding":false},{"id":1070132,"name":"Camden Jones","orcid":null,"position":4,"is_corresponding":false},{"id":1115249,"name":"Andrew Schacht","orcid":"0000-0002-7998-393X","position":5,"is_corresponding":false},{"id":263718,"name":"Xinghui Sun","orcid":"0000-0002-1156-0375","position":6,"is_corresponding":false},{"id":743530,"name":"Limei Zhang","orcid":"0000-0001-6807-5103","position":7,"is_corresponding":false},{"id":743527,"name":"Tao Wan","orcid":"0000-0003-1833-2540","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:19.266946Z","pmid":"37142222","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":[]}