RT Journal Article
SR Electronic
T1 A discriminator code-based DTD surveillance ensures faithful glycine delivery for protein biosynthesis in bacteria
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 322289
DO 10.1101/322289
A1 Santosh Kumar Kuncha
A1 Katta Suma
A1 Komal Ishwar Pawar
A1 Jotin Gogoi
A1 Satya Brata Routh
A1 Sambhavi Pottabathini
A1 Shobha P Kruparani
A1 Rajan Sankaranarayanan
YR 2018
UL http://biorxiv.org/content/early/2018/05/14/322289.abstract
AB 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, “reciprocally” in Bacteria and Eukarya, and suggests DTD’s strong selection pressure on bacterial tRNAGlys to retain a pyrimidine discriminator code.