Editing or proofreading domains of
aminoacyl-tRNA synthetases (AaRSs) hydrolyze misaminoacylated-tRNAs thereby
maintaining a high fidelity during translation. Archaeal threonyl-tRNA
synthetases (ThrRSs) possess an editing
domain that is unrelated to its eubacterial/eukaryotic counterparts. The domain
bears a striking structural homology to D-aminoacyl-tRNA deacylases (DTDs),
which remove D-amino acids charged on tRNA, that allowed us to propose a model
for perpetuation of homochirality in proteins. We earlier suggested that the
ThrRS editing domain from Pyrococcus
abyssi (Pab-NTD) does not use any
specific side chains for catalysis but employs a RNA-assisted water mediated
catalytic mechanism. In this talk, I will present some of our recent findings
on a crucial 'chiral proofreading' mechanism
by which D-amino acids are prevented by DTD from infiltrating the translational
machinery. We show how the enzyme has
been designed to be absolutely configuration-specific so that it does not
cross-react with the abundant L-aa-tRNA pool in the cell. Therefore, the study
highlights the importance of such fundamental enantioselection processes not
only in the early evolution of translational apparatus but also in the neuronal
context where some D-amino acids are present in high concentrations.