Department of Biochemistry & Molecular Genetics, School of Medicine, University of Colorado, 12801 E. 17th Avenue, Aurora, CO, 80045, USA.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Biomol NMR Assign. 2021 Oct;15(2):273-279. doi: 10.1007/s12104-021-10017-8. Epub 2021 Mar 19.
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.
真核细胞中一组 RNA 的腺苷酸到肌苷酸（A-to-I）编辑对于避免触发先天免疫系统是必需的。编辑由 ADAR1 进行，ADAR1 存在短（p110）和长（p150）两种异构体。ADAR1p150 主要位于细胞质中，具有 Z-RNA 结合结构域（Zα），仅在先天免疫反应期间表达。Zα 结构上同源的结构域，Zβ 结构域，在 N 端与 Zα 由一个长接头隔开，但它的功能仍不清楚。Zβ 不能单独与 RNA 结合，但包含 Zα、Zβ 和两个结构域之间的 95 个残基接头（Zα-Zβ）的片段的结合动力学与 Zα 单独相比明显不同。在这里，我们展示了来自 H. Sapiens ADAR1 的 Zα-Zβ 的溶液 NMR 骨架分配。基于化学位移预测的 Zα-Zβ 的二级结构与单独确定的 Zα 和 Zβ 的结构一致，并表明接头是固有无序的。将单独的 Zα 和 Zβ 结构域的化学位移与完整的 Zα-Zβ 结构进行比较表明，Zβ 可能与接头相互作用，但其功能目前尚不清楚。
