Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea.
To ensure a high fidelity during translation, threonyl-tRNA synthetases (ThrRSs) harbor an editing domain that removes noncognate L-serine attached to tRNAThr. Most archaeal ThrRSs possess a unique editing domain structurally similar to D-aminoacyl-tRNA deacylases (DTDs) found in eubacteria and eukaryotes that specifically removes D-amino acids attached to tRNA. Here, we provide mechanistic insights into the removal of noncognate L-serine from tRNAThr by a DTD-like editing module from Pyrococcus abyssi ThrRS (Pab-NTD). High-resolution crystal structures of Pab-NTD with pre- and post-transfer substrate analogs and with L-serine show mutually nonoverlapping binding sites for the seryl moiety. Although the pre-transfer editing is excluded, the analysis reveals the importance of main chain atoms in proper positioning of the post-transfer substrate for its hydrolysis. A single residue has been shown to play a pivotal role in the inversion of enantioselectivity both in Pab-NTD and DTD. The study identifies an enantioselectivity checkpoint that filters opposite chiral molecules and thus provides a fascinating example of how nature has subtly engineered this domain for the selection of chiral molecules during translation.
Hussain
Tanweer
T
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, India.
Kruparani
Shobha P
SP
Pal
Biswajit
B
Dock-Bregeon
Anne-Catherine
AC
Dwivedi
Shweta
S
Shekar
Megala R
MR
Sureshbabu
Kotini
K
Sankaranarayanan
Rajan
R
D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites; D008239:Lysine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D043903:Pyrococcus abyssi / Q000201:enzymology* / Q000235:genetics; D017393:RNA Editing; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry* / Q000235:genetics; D013237:Stereoisomerism; D013914:Threonine-tRNA Ligase / Q000737:chemistry* / Q000235:genetics; D046249:Transfer RNA Aminoacylation
D019843:Archaeal Proteins; D012346:RNA, Transfer, Amino Acyl; D013914:Threonine-tRNA Ligase; D008239:Lysine