CP1-dependent partitioning of pretransfer and posttransfer editing in leucyl-tRNA synthetase.
Mistranslation is toxic to bacterial and mammalian cells and can lead to neurodegeneration in the mouse. Mistranslation is caused by the attachment of the wrong amino acid to a specific tRNA. Many aminoacyl-tRNA synthetases have an editing activity that deacylates the mischarged amino acid before capture by the elongation factor and transport to the ribosome. For class I tRNA synthetases, the editing activity is encoded by the CP1 domain, which is distinct from the active site for aminoacylation. What is not clear is whether the enzymes also have an editing activity that is separable from CP1. A point mutation in CP1 of class I leucyl-tRNA synthetase inactivates deacylase activity and produces misacylated tRNA. In contrast, although deletion of the entire CP1 domain also disabled the deacylase activity, the deletion-bearing enzyme produced no mischarged tRNA. Further investigation showed that a second tRNA-dependent activity prevented misacylation and is intrinsic to the active site for aminoacylation.
Boniecki
Michal T
MT
Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61802, USA.
Vu
Michael T
MT
Betha
Aswini K
AK
Martinis
Susan A
SA
D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics*; D007935:Leucine-tRNA Ligase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D017354:Point Mutation; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D046249:Transfer RNA Aminoacylation
D012346:RNA, Transfer, Amino Acyl; D007935:Leucine-tRNA Ligase