{"doi":"10.1101/2020.12.20.423689","title":"Structures of the human mitochondrial ribosome recycling complexes reveal distinct mechanisms of recycling and antibiotic resistance","abstract":"Abstract Ribosomes are recycled for a new round of translation initiation by dissociation of ribosomal subunits, messenger RNA and transfer RNA from their translational post-termination complex. Mitochondrial ribosome recycling factor (RRF mt ) and a recycling-specific homolog of elongation factor G (EF-G2 mt ) are two proteins with mitochondria-specific additional sequences that catalyze the recycling step in human mitochondria. We have determined high-resolution cryo-EM structures of the human 55S mitochondrial ribosome (mitoribosome) in complex with RRF mt , and the mitoribosomal large 39S subunit in complex with both RRF mt and EF-G2 mt . In addition, we have captured the structure of a short-lived intermediate state of the 55S•RRF mt •EF-G2 mt complex. These structures clarify the role of a mitochondria-specific segment of RRF mt in mitoribosome recycling, identify the structural distinctions between the two isoforms of EF-G mt that confer their functional specificity, capture recycling-specific conformational changes in the L7/L12 stalk-base region, and suggest a distinct mechanistic sequence of events in mitoribosome recycling. Furthermore, biochemical and structural assessments of the sensitivity of EF-G2 mt to the antibiotic fusidic acid reveals that the molecular mechanism of antibiotic resistance for EF-G2 mt is markedly different from that exhibited by mitochondrial elongation factor EF-G1 mt , suggesting that these two homologous mitochondrial proteins have evolved diversely to negate the effect of a bacterial antibiotics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":125744,"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":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":572571,"name":"Ayush Deep","orcid":"0000-0003-0143-4479","position":1,"is_corresponding":false},{"id":573183,"name":"Ekansh K. Agrawal","orcid":null,"position":2,"is_corresponding":false},{"id":347703,"name":"Pooja Keshavan","orcid":"0000-0002-2344-4056","position":3,"is_corresponding":false},{"id":347704,"name":"Nilesh K. Banavali","orcid":"0000-0003-2206-7049","position":4,"is_corresponding":false},{"id":347705,"name":"Rajendra K. Agrawal","orcid":"0000-0001-9392-0065","position":5,"is_corresponding":false},{"id":347698,"name":"Ravi Kiran Koripella","orcid":"0000-0003-2901-1507","position":0,"is_corresponding":true}],"reference_count":90,"raw_metadata":null,"created_at":"2026-07-18T23:15:19.482428Z","pmid":null,"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":[]}