Distinct mechanisms of the human mitoribosome recycling and antibiotic resistance.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34127662.
- Also identified by DOI 10.1038/s41467-021-23726-4 and PMC identifier 8203779.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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. Here we present cryo-EM structures of the human 55S mitochondrial ribosome (mitoribosome) and the mitoribosomal large 39S subunit in complex with mitoribosome recycling factor (RRF<sub>mt</sub>) and a recycling-specific homolog of elongation factor G (EF-G2<sub>mt</sub>). These structures clarify an unusual role of a mitochondria-specific segment of RRF<sub>mt</sub>, identify the structural distinctions that confer functional specificity to EF-G2<sub>mt</sub>, and show that the deacylated tRNA remains with the dissociated 39S subunit, suggesting a distinct sequence of events in mitoribosome recycling. Furthermore, biochemical and structural analyses reveal that the molecular mechanism of antibiotic fusidic acid resistance for EF-G2<sub>mt</sub> is markedly different from that of mitochondrial elongation factor EF-G1<sub>mt</sub>, suggesting that the two human EF-G<sub>mt</sub>s have evolved diversely to negate the effect of a bacterial antibiotic.
Medical subject headings
- Drug Resistance, Microbial
- Mitochondrial Ribosomes
- Ribosomes