8B02

Crystal structure of the dsRBD domain of tRNA-dihydrouridine(20) synthase from Amphimedon queenslandica

8B02 の概要

• エントリーDOI: 10.2210/pdb8b02/pdb
• 分子名称: DRBM domain-containing protein, BETA-MERCAPTOETHANOL, CHLORIDE ION, ... (5 entities in total)
• 機能のキーワード: double-stranded rna-binding domain, rna binding protein, dihydrouridine synthase 2
• 由来する生物種: Amphimedon queenslandica
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 26677.06

構造登録者

Pecqueur, L.,Faivre, B.,Hamdane, D. (登録日: 2022-09-07, 公開日: 2022-11-30, 最終更新日: 2024-01-31)

主引用文献

Lombard, M.,Reed, C.J.,Pecqueur, L.,Faivre, B.,Toubdji, S.,Sudol, C.,Bregeon, D.,de Crecy-Lagard, V.,Hamdane, D.
Evolutionary Diversity of Dus2 Enzymes Reveals Novel Structural and Functional Features among Members of the RNA Dihydrouridine Synthases Family.
Biomolecules, 12:-, 2022

PubMed Abstract: Dihydrouridine (D) is an abundant modified base found in the tRNAs of most living organisms and was recently detected in eukaryotic mRNAs. This base confers significant conformational plasticity to RNA molecules. The dihydrouridine biosynthetic reaction is catalyzed by a large family of flavoenzymes, the dihydrouridine synthases (Dus). So far, only bacterial Dus enzymes and their complexes with tRNAs have been structurally characterized. Understanding the structure-function relationships of eukaryotic Dus proteins has been hampered by the paucity of structural data. Here, we combined extensive phylogenetic analysis with high-precision 3D molecular modeling of more than 30 Dus2 enzymes selected along the tree of life to determine the evolutionary molecular basis of D biosynthesis by these enzymes. Dus2 is the eukaryotic enzyme responsible for the synthesis of D20 in tRNAs and is involved in some human cancers and in the detoxification of β-amyloid peptides in Alzheimer's disease. In addition to the domains forming the canonical structure of all Dus, i.e., the catalytic TIM-barrel domain and the helical domain, both participating in RNA recognition in the bacterial Dus, a majority of Dus2 proteins harbor extensions at both ends. While these are mainly unstructured extensions on the N-terminal side, the C-terminal side extensions can adopt well-defined structures such as helices and beta-sheets or even form additional domains such as zinc finger domains. 3D models of Dus2/tRNA complexes were also generated. This study suggests that eukaryotic Dus2 proteins may have an advantage in tRNA recognition over their bacterial counterparts due to their modularity.

PubMed: 36551188
DOI: 10.3390/biom12121760

実験手法

X-RAY DIFFRACTION (1.676 Å)