Project Details
Projekt
Structural and functional analysis of the tRNA-modifying enzymes DNMT2 and tRNA-guanine-transglycosylase
Applicant
Professor Dr. Ralf Ficner
Subject Area
Structural Biology
Term
from 2015 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 277404908
At least 93 post-transcriptionally modified nucleosides have been identified in tRNAs. tRNA-modifying enzymes have to identify their cognate tRNA(s) and within the tRNA the site of modification. For many of these enzymes the structural requirements leading to their high specificity are yet unknown. The structural basis for the specificity of the eukaryotic methyltransferase DNMT2, which introduces a functionally important modification of C38, will be unraveled by the crystal structure analysis of a DNMT2-tRNA complex. This will also provide insights into the mechanism of stimulation of the methyltransferase activity by the hypermodified tRNA nucleoside queuosine at position 34 in the anticodon. With that respect, we will also study the eukaryotic tRNA-guanine-transglycosylase (TGT), which introduces queuine in tRNAs by replacing the guanine. The crystal structure of human TGT was just determined by us, and revealed unexpected differences in the quaternary structure with regard to the bacterial TGT. The resulting consequences concerning tRNA binding will be analyzed. Particularly open questions regarding the proposed regulation of TGT by phosphorylation will be addressed.
DFG Programme
Priority Programmes
