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The mechanism of error induction by the antibiotic viomycin provides insight into the fidelity mechanism of translation.
- Source :
-
ELife [Elife] 2019 Jun 07; Vol. 8. Date of Electronic Publication: 2019 Jun 07. - Publication Year :
- 2019
-
Abstract
- Applying pre-steady state kinetics to an Escherichia-coli- based reconstituted translation system, we have studied how the antibiotic viomycin affects the accuracy of genetic code reading. We find that viomycin binds to translating ribosomes associated with a ternary complex (TC) consisting of elongation factor Tu (EF-Tu), aminoacyl tRNA and GTP, and locks the otherwise dynamically flipping monitoring bases A1492 and A1493 into their active conformation. This effectively prevents dissociation of near- and non-cognate TCs from the ribosome, thereby enhancing errors in initial selection. Moreover, viomycin shuts down proofreading-based error correction. Our results imply a mechanism in which the accuracy of initial selection is achieved by larger backward rate constants toward TC dissociation rather than by a smaller rate constant for GTP hydrolysis for near- and non-cognate TCs. Additionally, our results demonstrate that translocation inhibition, rather than error induction, is the major cause of cell growth inhibition by viomycin.<br />Competing Interests: MH, CM, ME, SS No competing interests declared<br /> (© 2019, Holm et al.)
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 31172942
- Full Text :
- https://doi.org/10.7554/eLife.46124