Druggable differences: Targeting mechanistic differences between trans-translation and translation for selective antibiotic action

Pooja Srinivas, Kenneth C. Keiler, Christine M. Dunham

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Bacteria use trans-translation to rescue stalled ribosomes and target incomplete proteins for proteolysis. Despite similarities between tRNAs and transfer-messenger RNA (tmRNA), the key molecule for trans-translation, new structural and biochemical data show important differences between translation and trans-translation at most steps of the pathways. tmRNA and its binding partner, SmpB, bind in the A site of the ribosome but do not trigger the same movements of nucleotides in the rRNA that are required for codon recognition by tRNA. tmRNA-SmpB moves from the A site to the P site of the ribosome without subunit rotation to generate hybrid states, and moves from the P site to a site outside the ribosome instead of to the E site. During catalysis, transpeptidation to tmRNA appears to require the ribosomal protein bL27, which is dispensable for translation, suggesting that this protein may be conserved in bacteria due to trans-translation. These differences provide insights into the fundamental nature of trans-translation, and provide targets for new antibiotics that may have decrease cross-reactivity with eukaryotic ribosomes.

Original languageEnglish (US)
Article number2200046
JournalBioEssays
Volume44
Issue number8
DOIs
StatePublished - Aug 2022

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

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