Details
| Original language | English |
|---|---|
| Article number | e1006979 |
| Number of pages | 14 |
| Journal | PLoS Computational Biology |
| Volume | 15 |
| Issue number | 8 |
| Publication status | Published - 1 Aug 2019 |
| Externally published | Yes |
Abstract
Regulation and maintenance of protein synthesis are vital to all organisms and are thus key targets of attack and defense at the cellular level. Here, we mathematically analyze protein synthesis for its sensitivity to the inhibition of elongation factor EF-Tu and/or ribosomes in dependence of the system’s tRNA and codon compositions. We find that protein synthesis reacts ultrasensitively to a decrease in the elongation factor’s concentration for systems with an imbalance between codon usages and tRNA concentrations. For well-balanced tRNA/codon compositions, protein synthesis is impeded more effectively by the inhibition of ribosomes instead of EF-Tu. Our predictions are supported by re-evaluated experimental data as well as by independent computer simulations. Not only does the described ultrasensitivity render EF-Tu a distinguished target of protein synthesis inhibiting antibiotics. It may also enable persister cell formation mediated by toxin-antitoxin systems. The strong impact of the tRNA/codon composition provides a basis for tissue-specificities of disorders caused by mutations of human mitochondrial EF-Tu as well as for the potential use of EF-Tu targeting drugs for tissue-specific treatments.
ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Ecology, Evolution, Behavior and Systematics
- Mathematics(all)
- Modelling and Simulation
- Environmental Science(all)
- Ecology
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Genetics
- Neuroscience(all)
- Cellular and Molecular Neuroscience
- Computer Science(all)
- Computational Theory and Mathematics
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In: PLoS Computational Biology, Vol. 15, No. 8, e1006979, 01.08.2019.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Efficiency of protein synthesis inhibition depends on tRNA and codon compositions
AU - Rudorf, Sophia
N1 - Publisher Copyright: © 2019 Sophia Rudorf. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Regulation and maintenance of protein synthesis are vital to all organisms and are thus key targets of attack and defense at the cellular level. Here, we mathematically analyze protein synthesis for its sensitivity to the inhibition of elongation factor EF-Tu and/or ribosomes in dependence of the system’s tRNA and codon compositions. We find that protein synthesis reacts ultrasensitively to a decrease in the elongation factor’s concentration for systems with an imbalance between codon usages and tRNA concentrations. For well-balanced tRNA/codon compositions, protein synthesis is impeded more effectively by the inhibition of ribosomes instead of EF-Tu. Our predictions are supported by re-evaluated experimental data as well as by independent computer simulations. Not only does the described ultrasensitivity render EF-Tu a distinguished target of protein synthesis inhibiting antibiotics. It may also enable persister cell formation mediated by toxin-antitoxin systems. The strong impact of the tRNA/codon composition provides a basis for tissue-specificities of disorders caused by mutations of human mitochondrial EF-Tu as well as for the potential use of EF-Tu targeting drugs for tissue-specific treatments.
AB - Regulation and maintenance of protein synthesis are vital to all organisms and are thus key targets of attack and defense at the cellular level. Here, we mathematically analyze protein synthesis for its sensitivity to the inhibition of elongation factor EF-Tu and/or ribosomes in dependence of the system’s tRNA and codon compositions. We find that protein synthesis reacts ultrasensitively to a decrease in the elongation factor’s concentration for systems with an imbalance between codon usages and tRNA concentrations. For well-balanced tRNA/codon compositions, protein synthesis is impeded more effectively by the inhibition of ribosomes instead of EF-Tu. Our predictions are supported by re-evaluated experimental data as well as by independent computer simulations. Not only does the described ultrasensitivity render EF-Tu a distinguished target of protein synthesis inhibiting antibiotics. It may also enable persister cell formation mediated by toxin-antitoxin systems. The strong impact of the tRNA/codon composition provides a basis for tissue-specificities of disorders caused by mutations of human mitochondrial EF-Tu as well as for the potential use of EF-Tu targeting drugs for tissue-specific treatments.
UR - http://www.scopus.com/inward/record.url?scp=85071352365&partnerID=8YFLogxK
U2 - 10.1371/journal.pcbi.1006979
DO - 10.1371/journal.pcbi.1006979
M3 - Article
VL - 15
JO - PLoS Computational Biology
JF - PLoS Computational Biology
SN - 1553-734X
IS - 8
M1 - e1006979
ER -