5ED1

Human Adenosine Deaminase Acting on dsRNA (ADAR2) mutant E488Q bound to dsRNA sequence derived from S. cerevisiae BDF2 gene

Summary for 5ED1

• Entry DOI: 10.2210/pdb5ed1/pdb
• Related: 5ED2
• Descriptor: Double-stranded RNA-specific editase 1, RNA (5'-R(*UP*UP*CP*CP*CP*CP*AP*CP*AP*UP*UP*(8AZ)P*GP*AP*CP*GP*UP*UP*CP*AP*GP*UP*C)-3'), RNA (5'-R(*GP*AP*CP*UP*GP*AP*AP*CP*GP*AP*CP*CP*AP*AP*UP*GP*UP*GP*GP*GP*GP*AP*A)-3'), ... (6 entities in total)
• Functional Keywords: deaminase, human, hydrolase-rna complex, hydrolase/rna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 106174.54

Authors

Matthews, M.M.,Fisher, A.J.,Beal, P.A. (deposition date: 2015-10-20, release date: 2016-04-13, Last modification date: 2023-09-27)

Primary citation

Matthews, M.M.,Thomas, J.M.,Zheng, Y.,Tran, K.,Phelps, K.J.,Scott, A.I.,Havel, J.,Fisher, A.J.,Beal, P.A.
Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity.
Nat.Struct.Mol.Biol., 23:426-433, 2016

PubMed Abstract: Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. Here we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.

PubMed: 27065196
DOI: 10.1038/nsmb.3203

Experimental method

X-RAY DIFFRACTION (2.77 Å)