View source for 2gxb


==Crystal Structure of The Za Domain bound to Z-RNA==
<StructureSection load='2gxb' size='340' side='right'caption='[[2gxb]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2gxb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GXB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GXB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2gxb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gxb OCA], [https://pdbe.org/2gxb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gxb RCSB], [https://www.ebi.ac.uk/pdbsum/2gxb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gxb ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/DSRAD_HUMAN DSRAD_HUMAN] Defects in ADAR are a cause of dyschromatosis symmetrical hereditaria (DSH) [MIM:[https://omim.org/entry/127400 127400]; also known as reticulate acropigmentation of Dohi. DSH is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal parts of the hands and feet.<ref>PMID:12916015</ref> <ref>PMID:15146470</ref> <ref>PMID:15659327</ref> 
== Function ==
[https://www.uniprot.org/uniprot/DSRAD_HUMAN DSRAD_HUMAN] Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing-independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication.<ref>PMID:15556947</ref> <ref>PMID:15858013</ref> <ref>PMID:16475990</ref> <ref>PMID:17079286</ref> <ref>PMID:19710021</ref> <ref>PMID:19605474</ref> <ref>PMID:19651874</ref> <ref>PMID:19908260</ref> <ref>PMID:21289159</ref> <ref>PMID:22278222</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gx/2gxb_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gxb ConSurf].
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== Publication Abstract from PubMed ==
The A form RNA double helix can be transformed to a left-handed helix, called Z-RNA. Currently, little is known about the detailed structural features of Z-RNA or its involvement in cellular processes. The discovery that certain interferon-response proteins have domains that can stabilize Z-RNA as well as Z-DNA opens the way for the study of Z-RNA. Here, we present the 2.25 A crystal structure of the Zalpha domain of the RNA-editing enzyme ADAR1 (double-stranded RNA adenosine deaminase) complexed to a dUr(CG)(3) duplex RNA. The Z-RNA helix is associated with a unique solvent pattern that distinguishes it from the otherwise similar conformation of Z-DNA. Based on the structure, we propose a model suggesting how differences in solvation lead to two types of Z-RNA structures. The interaction of Zalpha with Z-RNA demonstrates how the interferon-induced isoform of ADAR1 could be targeted toward selected dsRNAs containing purine-pyrimidine repeats, possibly of viral origin.

A left-handed RNA double helix bound by the Z alpha domain of the RNA-editing enzyme ADAR1.,Placido D, Brown BA 2nd, Lowenhaupt K, Rich A, Athanasiadis A Structure. 2007 Apr;15(4):395-404. PMID:17437712<ref>PMID:17437712</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2gxb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adenosine deaminase 3D structures|Adenosine deaminase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Athanasiadis A]]
[[Category: Placido D]]
[[Category: Rich A]]