Role of D-aminoacyl-tRNA deacylase beyond chiral proofreading as a cellular defense against glycine mischarging by AlaRS
- CSIR-Centre for Cellular and Molecular Biology, India
Abstract
Strict L-chiral rejection through Gly-cisPro motif during chiral proofreading underlies inability of D-aminoacyl-tRNA deacylase (DTD) to discriminate between D-amino acids and achiral glycine. The consequent Gly-tRNAGly 'misediting paradox' is resolved by EF-Tu in the cell. Here, we show that DTD’s active site architecture can efficiently edit mischarged Gly-tRNAAla species four orders of magnitude more efficiently than even AlaRS, the only ubiquitous cellular checkpoint known for clearing the error. Also, DTD knockout in AlaRS editing-defective background causes pronounced toxicity in Escherichia coli even at low glycine levels which is alleviated by alanine supplementation. We further demonstrate that DTD positively selects the universally invariant tRNAAla-specific G3•U70. Moreover, DTD’s activity on non-cognate Gly-tRNAAla is conserved across all bacteria and eukaryotes, suggesting DTD’s key cellular role as a glycine deacylator. Our study thus reveals a hitherto unknown function of DTD in cracking the universal mechanistic dilemma encountered by AlaRS, and its physiological importance.
Article and author information
Author details
Rajan Sankaranarayanan
Funding
Council of Scientific and Industrial Research (12th Five Year Plan Project BSC0113)
- Rajan Sankaranarayanan
Science and Engineering Research Board (JC Bose Fellowship)
- Rajan Sankaranarayanan
Department of Biotechnology , Ministry of Science and Technology (Centre of Excellence)
- Rajan Sankaranarayanan
Council of Scientific and Industrial Research (Research Fellowship)
- Komal Ishwar Pawar
- Satya Brata Routh
Department of Biotechnology , Ministry of Science and Technology (Research Associateship)
- Katta Suma
Department of Biotechnology , Ministry of Science and Technology (INSPIRE Fellowship)
- 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
© 2017, Pawar 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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Role of D-aminoacyl-tRNA deacylase beyond chiral proofreading as a cellular defense against glycine mischarging by AlaRS
eLife 6:e24001.
https://doi.org/10.7554/eLife.24001
