4WFT

Crystal structure of tRNA-dihydrouridine(20) synthase dsRBD domain

Summary for 4WFT

• Entry DOI: 10.2210/pdb4wft/pdb
• Descriptor: tRNA-dihydrouridine(20) synthase [NAD(P)+]-like (2 entities in total)
• Functional Keywords: rna binding protein oxidoreductase, rna binding protein
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q9NX74
• Total number of polymer chains: 3
• Total formula weight: 41186.09

Authors

Bou-Nader, C.,Pecqueur, L.,Kamah, A.,Bregeon, D.,Golinelli-Pimpaneau, B.,Guimaraes, B.G.,Fontecave, M.,Hamdane, D. (deposition date: 2014-09-17, release date: 2015-10-07, Last modification date: 2023-11-08)

Primary citation

Bou-Nader, C.,Pecqueur, L.,Bregeon, D.,Kamah, A.,Guerineau, V.,Golinelli-Pimpaneau, B.,Guimaraes, B.G.,Fontecave, M.,Hamdane, D.
An extended dsRBD is required for post-transcriptional modification in human tRNAs.
Nucleic Acids Res., 43:9446-9456, 2015

PubMed Abstract: In tRNA, dihydrouridine is a conserved modified base generated by the post-transcriptional reduction of uridine. Formation of dihydrouridine 20, located in the D-loop, is catalyzed by dihydrouridine synthase 2 (Dus2). Human Dus2 (HsDus2) expression is upregulated in lung cancers, offering a growth advantage throughout its ability to interact with components of the translation apparatus and inhibit apoptosis. Here, we report the crystal structure of the individual domains of HsDus2 and their functional characterization. HsDus2 is organized into three major modules. The N-terminal catalytic domain contains the flavin cofactor involved in the reduction of uridine. The second module is the conserved α-helical domain known as the tRNA binding domain in HsDus2 homologues. It is connected via a flexible linker to an unusual extended version of a dsRNA binding domain (dsRBD). Enzymatic assays and yeast complementation showed that the catalytic domain binds selectively NADPH but cannot reduce uridine in the absence of the dsRBD. While in Dus enzymes from bacteria, plants and fungi, tRNA binding is essentially achieved by the α-helical domain, we showed that in HsDus2 this function is carried out by the dsRBD. This is the first reported case of a tRNA-modifying enzyme carrying a dsRBD used to bind tRNAs.

PubMed: 26429968
DOI: 10.1093/nar/gkv989

Experimental method

X-RAY DIFFRACTION (1.7 Å)