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

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.

SUBMITTER: Srinivas P

PROVIDER: S-EPMC9308750 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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

Srinivas Pooja P Keiler Kenneth C KC Dunham Christine M CM

BioEssays : news and reviews in molecular, cellular and developmental biology 20220619 8

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 ...[more]

PMID: 35719031

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Dataset Information

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

Publications

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

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