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Start Over Author "Zhang, Jingji" Journal nucleic acids research
9 results on '"Zhang, Jingji"'

4. Uncovering translation roadblocks during the development of a synthetic tRNA

Author

Prabhakar, Arjun, primary, Krahn, Natalie, additional, Zhang, Jingji, additional, Vargas-Rodriguez, Oscar, additional, Krupkin, Miri, additional, Fu, Ziao, additional, Acosta-Reyes, Francisco J, additional, Ge, Xueliang, additional, Choi, Junhong, additional, Crnković, Ana, additional, Ehrenberg, Måns, additional, Puglisi, Elisabetta Viani, additional, Söll, Dieter, additional, and Puglisi, Joseph, additional

Published
2022
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9. Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg2+ ions.

Author

Zhang J, Pavlov MY, and Ehrenberg M

Subjects
Bacterial Proteins biosynthesis, Bacterial Proteins genetics, Cations, Divalent, Codon, Escherichia coli genetics, Escherichia coli metabolism, Gentamicins pharmacology, Kinetics, Neomycin pharmacology, Paromomycin pharmacology, Peptide Elongation Factor Tu genetics, Peptide Elongation Factor Tu metabolism, RNA, Ribosomal, 16S genetics, RNA, Ribosomal, 16S metabolism, RNA, Transfer, Amino Acyl genetics, RNA, Transfer, Amino Acyl metabolism, Ribosomes genetics, Ribosomes metabolism, Subcellular Fractions chemistry, Subcellular Fractions drug effects, Subcellular Fractions metabolism, Anti-Bacterial Agents pharmacology, Escherichia coli drug effects, Genetic Code, Magnesium pharmacology, Protein Biosynthesis drug effects, Ribosomes drug effects
Abstract

We studied the effects of aminoglycosides and changing Mg2+ ion concentration on the accuracy of initial codon selection by aminoacyl-tRNA in ternary complex with elongation factor Tu and GTP (T3) on mRNA programmed ribosomes. Aminoglycosides decrease the accuracy by changing the equilibrium constants of 'monitoring bases' A1492, A1493 and G530 in 16S rRNA in favor of their 'activated' state by large, aminoglycoside-specific factors, which are the same for cognate and near-cognate codons. Increasing Mg2+ concentration decreases the accuracy by slowing dissociation of T3 from its initial codon- and aminoglycoside-independent binding state on the ribosome. The distinct accuracy-corrupting mechanisms for aminoglycosides and Mg2+ ions prompted us to re-interpret previous biochemical experiments and functional implications of existing high resolution ribosome structures. We estimate the upper thermodynamic limit to the accuracy, the 'intrinsic selectivity' of the ribosome. We conclude that aminoglycosides do not alter the intrinsic selectivity but reduce the fraction of it that is expressed as the accuracy of initial selection. We suggest that induced fit increases the accuracy and speed of codon reading at unaltered intrinsic selectivity of the ribosome.

Published
2018
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