Oral Presentation 2014 International Biophysics Congress

Chiral proofreading during translation of the genetic code (#87)

Rajan Sankaranarayanan 1
  1. Centre for Cellular and Molecular Biology, Hyderabad, Andhra Pradesh, India
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.