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A discriminator code–based DTD surveillance ensures faithful glycine delivery for protein biosynthesis in bacteria

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Cite as: eLife 2018;7:e38232 doi: 10.7554/eLife.38232

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.

Article and author information

Author details

  1. Santosh Kumar Kuncha

    CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Katta Suma

    CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    The authors declare that no competing interests exist.
  3. Komal Ishwar Pawar

    CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-1968-9851
  4. Jotin Gogoi

    CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    The authors declare that no competing interests exist.
  5. Satya Brata Routh

    CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    The authors declare that no competing interests exist.
  6. Sambhavi Pottabathini

    CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    The authors declare that no competing interests exist.
  7. Shobha P Kruparani

    CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
    Competing interests
    The authors declare that no competing interests exist.
  8. Rajan Sankaranarayanan

    CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India
    For correspondence
    sankar@ccmb.res.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-4524-9953

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.

Reviewing Editor

  1. Jonathan P Staley, Reviewing Editor, University of Chicago, United States

Publication history

  1. Received: May 14, 2018
  2. Accepted: August 7, 2018
  3. Accepted Manuscript published: August 9, 2018 (version 1)

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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