A discriminator code–based DTD surveillance ensures faithful glycine delivery for protein biosynthesis in bacteria
- CSIR-Centre for Cellular and Molecular Biology, India
Abstract
D-aminoacyl-tRNA deacylase (DTD) acts on achiral glycine, in addition to D-amino acids, attached to tRNA. We have recently shown that this activity enables DTD to clear non-cognate Gly-tRNAAla with 1000-fold higher efficiency than its activity on Gly-tRNAGly, indicating tRNA-based modulation of DTD (Pawar et al., 2017). Here, we show that tRNA's discriminator base predominantly accounts for this activity difference and is the key to selection by DTD. Accordingly, the uracil discriminator base, serving as a negative determinant, prevents Gly-tRNAGly misediting by DTD and this protection is augmented by EF-Tu. Intriguingly, eukaryotic DTD has inverted discriminator base specificity and uses only G3•U70 for tRNAGly/Ala discrimination. Moreover, DTD prevents alanine-to-glycine misincorporation in proteins rather than only recycling mischarged tRNAAla. Overall, the study reveals the unique co-evolution of DTD and discriminator base, and suggests DTD's strong selection pressure on bacterial tRNAGlys to retain a pyrimidine discriminator code.
Data availability
Biochemical data is available as a source data file. All other data are included in the manuscript and supporting files.
Article and author information
Author details
Komal Ishwar Pawar
Rajan Sankaranarayanan
Funding
Department of Biotechnology , Ministry of Science and Technology (Centre of Excellence)
- Rajan Sankaranarayanan
Science and Engineering Research Board (J. C. Bose Fellowship)
- Rajan Sankaranarayanan
Department of Science and Technology, Ministry of Science and Technology (DST-INSPIRE)
- Santosh Kumar Kuncha
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Kuncha et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A discriminator code–based DTD surveillance ensures faithful glycine delivery for protein biosynthesis in bacteria
eLife 7:e38232.
https://doi.org/10.7554/eLife.38232
