9DP5

Crystal Structure of Hydra Adenosine Deaminase Acting on RNA (ADAR) Deaminase Domain

Summary for 9DP5

• Entry DOI: 10.2210/pdb9dp5/pdb
• Descriptor: Double-stranded RNA-specific editase Adar-like, ZINC ION, INOSITOL HEXAKISPHOSPHATE, ... (6 entities in total)
• Functional Keywords: rna editing, deaminase, adenosine, inosine, adar, rna binding protein
• Biological source: Hydra vulgaris (swiftwater hydra)
• Total number of polymer chains: 2
• Total formula weight: 85057.87

Authors

Fisher, A.J.,Wilcox, X.E. (deposition date: 2024-09-20, release date: 2025-03-26)

Primary citation

Wilcox, X.E.,Zhang, H.,Mah, J.L.,Cazet, J.F.,Mozumder, S.,Venkatesh, S.,Juliano, C.E.,Beal, P.A.,Fisher, A.J.
Phylogenetic and structural analysis of Hydra ADAR.
Arch.Biochem.Biophys., 767:110353-110353, 2025

PubMed Abstract: Adenosine deaminases acting on RNAs (ADARs) perform adenosine-to-inosine (A-to-I) RNA editing for essential biological functions. While studies of editing sites in diverse animals have revealed unique biological roles of ADAR editing including temperature adaptation and reproductive maturation, rigorous biochemical and structural studies of these ADARs are lacking. Here, we present a phylogenetic sequence analysis and AlphaFold computational structure prediction to reveal that medusozoan ADAR2s contain five dsRNA binding domains (dsRBDs) with several RNA binding residues in the dsRBDs and deaminase domain conserved. Additionally, we identified evolutionary divergence between the medusozoan (e.g. Hydra) and anthozoan cnidarian subphyla. The anthozoan ADAR deaminase domains more closely resemble human ADARs with longer 5' RNA binding loops, glutamate base-flipping residues, and a conserved TWDG dimerization motif. Conversely, medusozoan ADAR deaminase domains have short 5' binding loops, glutamine flipping residues, and non-conserved helix dimerization motif. We also report the direct detection of A-to-I RNA editing by an ADAR ortholog from the freshwater cnidarian Hydra vulgaris (hyADAR). We solved the crystal structure of the monomeric deaminase domain of hyADAR (hyADARd) to 2.0 Å resolution, showing conserved active site architecture and the presence of a buried inositol hexakisphosphate known to be required for ADAR activity. In addition, these data demonstrate that medusozoans have evolved novel ADAR structural features, however the physiological consequence of this remains unknown. In addition, these results provide a framework for biochemically and structurally characterizing ADARs from evolutionarily distant organisms to understand the diverse roles of ADAR editing amongst metazoans.

PubMed: 39986343
DOI: 10.1016/j.abb.2025.110353

Experimental method

X-RAY DIFFRACTION (1.998 Å)