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

• Published in: Nature communications 2018-02, Vol.9 (1), p.511-13, Article 511
• Main Authors: Kuncha, Santosh Kumar, Mazeed, Mohd, Singh, Raghvendra, Kattula, Bhavita, Routh, Satya Brata, Sankaranarayanan, Rajan
• Format: Article
• Language: English
• Subjects: 631/337/574/1793; 631/45/173; 631/535/1266; Alanine; Alanine - chemistry; Alanine - genetics; Alanine - metabolism; Amino Acid Sequence; Amino acids; Aminoacyltransferases - chemistry; Aminoacyltransferases - genetics; Aminoacyltransferases - metabolism; Animalia; Animals; Apicomplexa - genetics; Apicomplexa - metabolism; Bacteria; Bacteria - genetics; Bacteria - metabolism; Binding Sites; Biological Evolution; Catalysis; Cloning, Molecular; Crystal structure; Crystallography, X-Ray; Cyanobacteria; D-Amino acids; E coli; Editing; Enzymes; Gene Expression; Genomes; Glycine; Humanities and Social Sciences; Humans; L-Alanine; Models, Molecular; multidisciplinary; Phylogenetics; Proofreading; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Proteins; Quality control; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; RNA, Transfer, Amino Acyl - chemistry; RNA, Transfer, Amino Acyl - genetics; RNA, Transfer, Amino Acyl - metabolism; Science; Science (multidisciplinary); Selectivity; Sequence Alignment; Sequence Homology, Amino Acid; Substrate Specificity; Threonine - chemistry; Threonine - genetics; Threonine - metabolism; Transfer RNA Aminoacylation - genetics; tRNA
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-02204-w

D-aminoacyl-tRNA deacylase (DTD), a bacterial/eukaryotic trans -editing factor, removes d -amino acids mischarged on tRNAs and achiral glycine mischarged on tRNA Ala . An invariant cross-subunit Gly- cis Pro 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 ( A nimalia-specific t RNA d eacylase), that harbors a Gly- trans Pro 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 tRNA Thr (G4•U69) by eukaryotic AlaRS. The proofreading activity of ATD is conserved across diverse classes of phylum Chordata. Animalia genomes enriched in tRNA Thr (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. The number of tRNA isodecoders has expanded significantly during evolution, which has resulted in ambiguity in tRNA selection by synthetases. Here the authors identify and characterize a dedicated proofreading factor that eliminates errors caused by ambiguity in tRNA selection by eukaryotic tRNA synthetases.