Evolutionary Diversity of Dus2 Enzymes Reveals Novel Structural and Functional Features among Members of the RNA Dihydrouridine Synthases Family - Laboratoire de Chimie des Processus Biologiques Accéder directement au contenu
Article Dans Une Revue Biomolecules Année : 2022

Evolutionary Diversity of Dus2 Enzymes Reveals Novel Structural and Functional Features among Members of the RNA Dihydrouridine Synthases Family

Colbie J Reed
  • Fonction : Auteur
Ludovic Pecqueur
Bruno Faivre
Sabrine Toubdji
  • Fonction : Auteur
Claudia Sudol
  • Fonction : Auteur
Damien Brégeon
Valérie de Crécy-Lagard
Djemel Hamdane

Résumé

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.
Fichier principal
Vignette du fichier
biomolecules-12-01760-v2.pdf (5.12 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-04238858 , version 1 (12-10-2023)

Identifiants

Citer

Murielle Lombard, Colbie J Reed, Ludovic Pecqueur, Bruno Faivre, Sabrine Toubdji, et al.. Evolutionary Diversity of Dus2 Enzymes Reveals Novel Structural and Functional Features among Members of the RNA Dihydrouridine Synthases Family. Biomolecules, 2022, 12 (12), pp.1760. ⟨10.3390/biom12121760⟩. ⟨hal-04238858⟩
21 Consultations
5 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More