A chiral selectivity relaxed paralog of DTD for proofreading tRNA mischarging in Animalia

Nat Commun. 2018 Feb 6;9(1):511. doi: 10.1038/s41467-017-02204-w.

Abstract

D-aminoacyl-tRNA deacylase (DTD), a bacterial/eukaryotic trans-editing factor, removes D-amino acids mischarged on tRNAs and achiral glycine mischarged on tRNAAla. An invariant cross-subunit Gly-cisPro motif forms the mechanistic basis of L-amino acid rejection from the catalytic site. Here, we present the identification of a DTD variant, named ATD (Animalia-specific tRNA deacylase), that harbors a Gly-transPro motif. The cis-to-trans switch causes a "gain of function" through L-chiral selectivity in ATD resulting in the clearing of L-alanine mischarged on tRNAThr(G4•U69) by eukaryotic AlaRS. The proofreading activity of ATD is conserved across diverse classes of phylum Chordata. Animalia genomes enriched in tRNAThr(G4•U69) genes are in strict association with the presence of ATD, underlining the mandatory requirement of a dedicated factor to proofread tRNA misaminoacylation. The study highlights the emergence of ATD during genome expansion as a key event associated with the evolution of Animalia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry*
  • Alanine / genetics
  • Alanine / metabolism
  • Amino Acid Sequence
  • Aminoacyltransferases / chemistry*
  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / metabolism
  • Animals
  • Apicomplexa / genetics
  • Apicomplexa / metabolism
  • Bacteria / genetics
  • Bacteria / metabolism
  • Binding Sites
  • Biological Evolution
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Gene Expression
  • Humans
  • Models, Molecular
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • RNA, Transfer, Amino Acyl / chemistry*
  • RNA, Transfer, Amino Acyl / genetics
  • RNA, Transfer, Amino Acyl / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Threonine / chemistry*
  • Threonine / genetics
  • Threonine / metabolism
  • Transfer RNA Aminoacylation / genetics*

Substances

  • RNA, Transfer, Amino Acyl
  • Recombinant Proteins
  • Threonine
  • Aminoacyltransferases
  • Alanine