5OC5

Crystal structure of human tRNA-dihydrouridine(20) synthase dsRBD K419A-K420A mutant

5OC5 の概要

• エントリーDOI: 10.2210/pdb5oc5/pdb
• 分子名称: tRNA-dihydrouridine(20) synthase [NAD(P)+]-like, GLYCEROL, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: double-stranded rna-binding domain, rna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13959.68

構造登録者

Bou-nader, C.,Pecqueur, L.,Hamdane, D. (登録日: 2017-06-29, 公開日: 2018-12-26, 最終更新日: 2024-01-17)

主引用文献

Bou-Nader, C.,Barraud, P.,Pecqueur, L.,Perez, J.,Velours, C.,Shepard, W.,Fontecave, M.,Tisne, C.,Hamdane, D.
Molecular basis for transfer RNA recognition by the double-stranded RNA-binding domain of human dihydrouridine synthase 2.
Nucleic Acids Res., 47:3117-3126, 2019

PubMed Abstract: Double stranded RNA-binding domain (dsRBD) is a ubiquitous domain specialized in the recognition of double-stranded RNAs (dsRNAs). Present in many proteins and enzymes involved in various functional roles of RNA metabolism, including RNA splicing, editing, and transport, dsRBD generally binds to RNAs that lack complex structures. However, this belief has recently been challenged by the discovery of a dsRBD serving as a major tRNA binding module for human dihydrouridine synthase 2 (hDus2), a flavoenzyme that catalyzes synthesis of dihydrouridine within the complex elbow structure of tRNA. We here unveil the molecular mechanism by which hDus2 dsRBD recognizes a tRNA ligand. By solving the crystal structure of this dsRBD in complex with a dsRNA together with extensive characterizations of its interaction with tRNA using mutagenesis, NMR and SAXS, we establish that while hDus2 dsRBD retains a conventional dsRNA recognition capability, the presence of an N-terminal extension appended to the canonical domain provides additional residues for binding tRNA in a structure-specific mode of action. Our results support that this extension represents a feature by which the dsRBD specializes in tRNA biology and more broadly highlight the importance of structural appendages to canonical domains in promoting the emergence of functional diversity.

PubMed: 30605527
DOI: 10.1093/nar/gky1302

実験手法

X-RAY DIFFRACTION (1.893 Å)