6VFF

Dimer of Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA sequence derived from human GLI1 gene

6VFF の概要

• エントリーDOI: 10.2210/pdb6vff/pdb
• 分子名称: Double-stranded RNA-specific editase 1, RNA (5-R(*GP*CP*UP*CP*GP*CP*GP*AP*UP*GP*CP*UP*(8AZ)P*GP*AP*GP*GP*GP*CP* UP*CP*UP*GP*AP*UP*AP*GP*CP*UP*AP*CP*G)-3), RNA(5-R(*CP*GP*UP*AP*GP*CP*UP*AP*UP*CP*AP*GP*AP*GP*CP*CP*CP*CP*CP*CP*AP*GP*CP*AP*UP*CP*GP*CP*GP*AP*GP*C)-3), ... (6 entities in total)
• 機能のキーワード: protein-rna complex, hydrolase, hydrolase-rna complex, hydrolase/rna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 129959.62

構造登録者

Thuy-boun, A.S.,Fisher, A.J.,Beal, P.A. (登録日: 2020-01-03, 公開日: 2020-07-01, 最終更新日: 2023-10-11)

主引用文献

Thuy-Boun, A.S.,Thomas, J.M.,Grajo, H.L.,Palumbo, C.M.,Park, S.,Nguyen, L.T.,Fisher, A.J.,Beal, P.A.
Asymmetric dimerization of adenosine deaminase acting on RNA facilitates substrate recognition.
Nucleic Acids Res., 48:7958-7972, 2020

PubMed Abstract: Adenosine deaminases acting on RNA (ADARs) are enzymes that convert adenosine to inosine in duplex RNA, a modification that exhibits a multitude of effects on RNA structure and function. Recent studies have identified ADAR1 as a potential cancer therapeutic target. ADARs are also important in the development of directed RNA editing therapeutics. A comprehensive understanding of the molecular mechanism of the ADAR reaction will advance efforts to develop ADAR inhibitors and new tools for directed RNA editing. Here we report the X-ray crystal structure of a fragment of human ADAR2 comprising its deaminase domain and double stranded RNA binding domain 2 (dsRBD2) bound to an RNA duplex as an asymmetric homodimer. We identified a highly conserved ADAR dimerization interface and validated the importance of these sequence elements on dimer formation via gel mobility shift assays and size exclusion chromatography. We also show that mutation in the dimerization interface inhibits editing in an RNA substrate-dependent manner for both ADAR1 and ADAR2.

PubMed: 32597966
DOI: 10.1093/nar/gkaa532

実験手法

X-RAY DIFFRACTION (2.8 Å)