6VFF

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

Summary for 6VFF

• Entry DOI: 10.2210/pdb6vff/pdb
• Descriptor: 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)
• Functional Keywords: protein-rna complex, hydrolase, hydrolase-rna complex, hydrolase/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 129959.62

Authors

Thuy-boun, A.S.,Fisher, A.J.,Beal, P.A. (deposition date: 2020-01-03, release date: 2020-07-01, Last modification date: 2023-10-11)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)