Adenosine-to-inosine (A-to-I) editing of a subset of RNAs in a eukaryotic cell is required in order to avoid triggering the innate immune system. Editing is carried out by ADAR1, which exists as short (p110) and long (p150) isoforms. ADAR1p150 is mostly cytoplasmic, possesses a Z-RNA binding domain (Zα), and is only expressed during the innate immune response. A structurally homologous domain to Zα, the Zβ domain, is separated by a long linker from Zα on the N-terminus of ADAR1 but its function remains unknown. Zβ does not bind to RNA in isolation, yet the binding kinetics of the segment encompassing Zα, Zβ and the 95-residue linker between the two domains (Zα-Zβ) are markedly different compared to Zα alone. Here we present the solution NMR backbone assignment of Zα-Zβ from H. Sapiens ADAR1. The predicted secondary structure of Zα-Zβ based on chemical shifts is in agreement with previously determined structures of Zα and Zβ in isolation, and indicates that the linker is intrinsically disordered. Comparison of the chemical shifts between the individual Zα and Zβ domains to the full Zα-Zβ construct suggests that Zβ may interact with the linker, the function of which is currently unknown.
Keywords: ADAR1; Backbone chemical shift assignment; Editing; Protein domains; Protein structure and dynamics; Z-RNA.
© 2021. The Author(s), under exclusive licence to Springer Nature B.V.