5HP3: Human Adenosine Deaminase Acting On Dsrna (adar2) Bound To Dsrna Sequence Derived From S. Cerevisiae Bdf2 Gene With Ac Mismatch At Reaction Site

Citation:
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.
PDB ID: 5HP3Download
MMDB ID: 138410
PDB Deposition Date: 2016/1/20
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 3.09  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 5HP3: trimeric; determined by author and by software (PISA)
Molecular Components in 5HP3
Label Count Molecule
Protein (1 molecule)
1
Double-stranded RNA-specific Editase 1(Gene symbol: ADARB1)
Molecule annotation
Nucleotides(2 molecules)
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')
Molecule annotation
1
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')
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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