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Hydrolase PDB id
2b7t
Jmol
Contents
Protein chain
73 a.a. *
* Residue conservation analysis
PDB id:
2b7t
Name: Hydrolase
Title: Structure of adar2 dsrbm1
Structure: Double-stranded RNA-specific editase 1. Chain: a. Fragment: double-stranded RNA-binding domain. Synonym: dsrna adenosine deaminase, RNA editing deaminase 1, RNA editing enzyme 1. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: adarb1, red1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
NMR struc: 20 models
Authors: R.Stefl,M.Xu,L.Skrisovska,R.B.Emeson,F.H.-T.Allain
Key ref:
R.Stefl et al. (2006). Structure and Specific RNA Binding of ADAR2 Double-Stranded RNA Binding Motifs. Structure, 14, 345-355. PubMed id: 16472753 DOI: 10.1016/j.str.2005.11.013
Date:
05-Oct-05     Release date:   14-Mar-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P51400  (RED1_RAT) -  Double-stranded RNA-specific editase 1
Seq:
Struc: 		 
Seq:
Struc: 		711 a.a.
73 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     intracellular   1 term 
  Biochemical function     RNA binding     2 terms  

 

 
DOI no: 10.1016/j.str.2005.11.013 Structure 14:345-355 (2006)
PubMed id: 16472753  
 
 
Structure and Specific RNA Binding of ADAR2 Double-Stranded RNA Binding Motifs.
R.Stefl, M.Xu, L.Skrisovska, R.B.Emeson, F.H.Allain.
 
  ABSTRACT  
 
Adenosine deaminases that act on RNA (ADARs) site-selectively modify adenosines to inosines within RNA transcripts, thereby recoding genomic information. How ADARs select specific adenosine moieties for deamination is poorly understood. Here, we report NMR structures of the two double-stranded RNA binding motifs (dsRBMs) of rat ADAR2 and an NMR chemical shift perturbation study of the interaction of the two dsRBMs with a 71 nucleotide RNA encoding the R/G site of the GluR-B. We have identified the protein and the RNA surfaces involved in complex formation, allowing us to present an NMR-based model of the complex. We have found that dsRBM1 recognizes a conserved pentaloop, whereas dsRBM2 recognizes two bulged bases adjacent to the editing site, demonstrating RNA structure-dependent recognition by the ADAR2 dsRBMs. In vitro mutagenesis studies with both the protein and the RNA further support our structural findings.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. RNA Binding Surfaces of ADAR2 dsRBMs
(A-C) dsRBM1-R/G central loop. (A) Overlay of [1H-15N]-HSQC spectra of dsRBM1 (in red) and the dsRBM1-R/G central loop complex (in blue). (B) Chemical shift changes (Dd) for dsRBM1 upon addition of the R/G central loop. The Dd is calculated as ([w[HN]Dd[HN]]2 + [w[N]Dd[N]]2)1/2, where w[HN] = 1 and w[N] = 0.154 are weight factors of the nucleus (Mulder et al., 1999); asterisk, proline. (C) Dd upon RNA binding mapped to the surface of the protein identifies the RNA binding surface of dsRBM1 (left; in red; Dd >= 0.15 are displayed). The electrostatic surface of dsRBM1 (right).
(D-F) dsRBM2-R/G irregular duplex. (D) Overlay of [1H-15N]-HSQC spectra of dsRBM2 (in green) and the dsRBM2-R/G irregular duplex complex (in blue). (E) Dd for dsRBM2 upon addition of R/G irregular duplex (asterisk, proline; closed, black circle, unassigned). (F) Dd upon RNA binding mapped to the surface of the protein identifies the RNA binding surface of dsRBM2 (left; in green). The electrostatic surface of dsRBM2 (right).
 
  The above figure is reprinted by permission from Cell Press: Structure (2006, 14, 345-355) copyright 2006.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21182352 C.X.George, Z.Gan, Y.Liu, and C.E.Samuel (2011).
Adenosine deaminases acting on RNA, RNA editing, and interferon action.
  J Interferon Cytokine Res, 31, 99.  
21080422 S.Yamashita, T.Nagata, M.Kawazoe, C.Takemoto, T.Kigawa, P.Güntert, N.Kobayashi, T.Terada, M.Shirouzu, M.Wakiyama, Y.Muto, and S.Yokoyama (2011).
Structures of the first and second double-stranded RNA-binding domains of human TAR RNA-binding protein.
  Protein Sci, 20, 118-130.  
20192758 K.Nishikura (2010).
Functions and regulation of RNA editing by ADAR deaminases.
  Annu Rev Biochem, 79, 321-349.  
19731047 P.Zhou, and G.Wagner (2010).
Overcoming the solubility limit with solubility-enhancement tags: successful applications in biomolecular NMR studies.
  J Biomol NMR, 46, 23-31.  
20946981 R.Stefl, F.C.Oberstrass, J.L.Hood, M.Jourdan, M.Zimmermann, L.Skrisovska, C.Maris, L.Peng, C.Hofr, R.B.Emeson, and F.H.Allain (2010).
The solution structure of the ADAR2 dsRBM-RNA complex reveals a sequence-specific readout of the minor groove.
  Cell, 143, 225-237.
PDB codes: 2l2j 2l2k 2l3c 2l3j
19480689 B.Z.Tan, H.Huang, R.Lam, and T.W.Soong (2009).
Dynamic regulation of RNA editing of ion channels and receptors in the mammalian nervous system.
  Mol Brain, 2, 13.  
19390115 J.P.Palavicini, M.A.O'Connell, and J.J.Rosenthal (2009).
An extra double-stranded RNA binding domain confers high activity to a squid RNA editing enzyme.
  RNA, 15, 1208-1218.  
19740768 M.Ensterö, C.Daniel, H.Wahlstedt, F.Major, and M.Ohman (2009).
Recognition and coupling of A-to-I edited sites are determined by the tertiary structure of the RNA.
  Nucleic Acids Res, 37, 6916-6926.  
19219738 P.Jayalath, S.Pokharel, E.Véliz, and P.A.Beal (2009).
Synthesis and evaluation of an RNA editing substrate bearing 2'-deoxy-2'-mercaptoadenosine.
  Nucleosides Nucleotides Nucleic Acids, 28, 78-88.  
18551175 M.N.Pouch-Pélissier, T.Pélissier, T.Elmayan, H.Vaucheret, D.Boko, M.F.Jantsch, and J.M.Deragon (2008).
SINE RNA induces severe developmental defects in Arabidopsis thaliana and interacts with HYL1 (DRB1), a key member of the DCL1 complex.
  PLoS Genet, 4, e1000096.  
17473849 B.M.Lunde, C.Moore, and G.Varani (2007).
RNA-binding proteins: modular design for efficient function.
  Nat Rev Mol Cell Biol, 8, 479-490.  
17437712 D.Placido, B.A.Brown, K.Lowenhaupt, A.Rich, and A.Athanasiadis (2007).
A left-handed RNA double helix bound by the Z alpha domain of the RNA-editing enzyme ADAR1.
  Structure, 15, 395-404.
PDB code: 2gxb
17629578 I.H.Greger, E.B.Ziff, and A.C.Penn (2007).
Molecular determinants of AMPA receptor subunit assembly.
  Trends Neurosci, 30, 407-416.  
17428802 L.Valente, and K.Nishikura (2007).
RNA binding-independent dimerization of adenosine deaminases acting on RNA and dominant negative effects of nonfunctional subunits on dimer functions.
  J Biol Chem, 282, 16054-16061.  
17139332 K.Nishikura (2006).
Editor meets silencer: crosstalk between RNA editing and RNA interference.
  Nat Rev Mol Cell Biol, 7, 919-931.  
16672376 M.Xu, K.S.Wells, and R.B.Emeson (2006).
Substrate-dependent contribution of double-stranded RNA-binding motifs to ADAR2 function.
  Mol Biol Cell, 17, 3211-3220.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.