{"doi":"10.1042/bst20253084","title":"Multifaceted roles of mycobacterial HflX: ribosome splitting, rRNA disordering, and drug resistance","abstract":"High frequency of lysogenization X (HflX) is an enigmatic protein that has been implicated in rescuing translationally stalled ribosomes and macrolide-lincosamide antibiotic resistance, as well as in ribosome biogenesis. The protein shows significant sequence and structural variation across species, including variation among paralogs within the same organism. Recent cryo-EM structure determination of ribosome-HflX complexes from different eubacterial species has provided important mechanistic clues to HflX function. Mycobacterial HflXs carry a distinct N-terminal extension (NTE) and a small insertion, as compared with their eubacterial homologs, suggesting that the mycobacterial HflX could have distinct functional mechanisms. This article presents a brief overview of these studies highlighting (i) what we have learned from recent multiple mycobacterial ribosome-HflX complex structures and (ii) the roles of mycobacteria-specific segments in ribosomal RNA disordering that leads to ribosome splitting to rescue translation by removing the drug-bound stalled ribosome from the translationally active polysome pool. Future studies needed to resolve some of the outstanding issues related to HflX function and dynamics are also discussed.","journal":"Biochemical Society Transactions","year":2025,"id":572856,"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":0.957,"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":734091,"name":"Pallavi Ghosh","orcid":"0000-0002-1622-7301","position":1,"is_corresponding":false},{"id":347705,"name":"Rajendra K. Agrawal","orcid":"0000-0001-9392-0065","position":2,"is_corresponding":false},{"id":999133,"name":"Soneya Majumdar","orcid":"0000-0002-6518-9057","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:57:27.876396Z","pmid":"40833115","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":[]}