5ED2

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

Summary for 5ED2

• Entry DOI: 10.2210/pdb5ed2/pdb
• Related: 5ED1
• Descriptor: Double-stranded RNA-specific editase 1, RNA (5'-R(P*GP*CP*UP*CP*GP*CP*GP*AP*UP*GP*CP*UP*(8AZ)P*GP*AP*GP*GP*GP*CP*UP*CP*UP*G)-3'), RNA (5'-R(P*CP*AP*GP*AP*GP*CP*CP*CP*CP*CP*CP*AP*GP*CP*AP*UP*CP*GP*CP*GP*AP*GP*C)-3'), ... (5 entities in total)
• Functional Keywords: deaminase, human, hydrolase-rna complex, hydrolase/rna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 120961.47

Authors

Matthews, M.M.,Fisher, A.J. (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 (2.95 Å)