Crystal Structure of the Human tRNA Guanine Transglycosylase Catalytic Subunit QTRT1

Biomolecules
Sven JohannssonR Ficner

Abstract

RNA modifications have been implicated in diverse and important roles in all kingdoms of life with over 100 of them present on tRNAs. A prominent modification at the wobble base of four tRNAs is the 7-deaza-guanine derivative queuine which substitutes the guanine at position 34. This exchange is catalyzed by members of the enzyme class of tRNA guanine transglycosylases (TGTs). These enzymes incorporate guanine substituents into tRNAAsp, tRNAAsn tRNAHis, and tRNATyr in all kingdoms of life. In contrast to the homodimeric bacterial TGT, the active eukaryotic TGT is a heterodimer in solution, comprised of a catalytic QTRT1 subunit and a noncatalytic QTRT2 subunit. Bacterial TGT enzymes, that incorporate a queuine precursor, have been identified or proposed as virulence factors for infections by pathogens in humans and therefore are valuable targets for drug design. To date no structure of a eukaryotic catalytic subunit is reported, and differences to its bacterial counterpart have to be deducted from sequence analysis and models. Here we report the first crystal structure of a eukaryotic QTRT1 subunit and compare it to known structures of the bacterial TGT and murine QTRT2. Furthermore, we were able to determine the crystal struct...Continue Reading

Citations

Mar 10, 2020·Chemical Communications : Chem Comm·Mashael A AlqasemVincent P Kelly
Jul 10, 2021·RNA Biology·Katharina SieversRalf Ficner

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Methods Mentioned

BETA
size exclusion chromatography
transglycosylation

Software Mentioned

Rosetta
PHENIX
package
CCP4
Coot
XDS
CCP4 suite
PHASER

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