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New page: left|200px<br /> <applet load="1qgp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1qgp" /> '''NMR STRUCTURE OF THE Z-ALPHA DOMAIN OF ADAR...
 
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[[Image:1qgp.gif|left|200px]]<br />
<applet load="1qgp" size="450" color="white" frame="true" align="right" spinBox="true"
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'''NMR STRUCTURE OF THE Z-ALPHA DOMAIN OF ADAR1, 15 STRUCTURES'''<br />


==Overview==
==NMR STRUCTURE OF THE Z-ALPHA DOMAIN OF ADAR1, 15 STRUCTURES==
Double-stranded RNA deaminase I (ADAR1) contains the Z-DNA binding domain, Zalpha. Here we report the solution structure of free Zalpha and map the, interaction surface with Z-DNA, confirming roles previously assigned to, residues by mutagenesis. Comparison with the crystal structure of the, (Zalpha)(2)/Z-DNA complex shows that most Z-DNA contacting residues in, free Zalpha are prepositioned to bind Z-DNA, thus minimizing the entropic, cost of binding. Comparison with homologous, (alpha+beta)helix-turn-helix/B-DNA complexes suggests that binding of, Zalpha to B-DNA is disfavored by steric hindrance, but does not eliminate, the possibility that related domains may bind to both B- and Z-DNA.
<StructureSection load='1qgp' size='340' side='right'caption='[[1qgp]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1qgp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1QGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1QGP FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1qgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1qgp OCA], [https://pdbe.org/1qgp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1qgp RCSB], [https://www.ebi.ac.uk/pdbsum/1qgp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1qgp 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/qg/1qgp_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=1qgp ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Double-stranded RNA deaminase I (ADAR1) contains the Z-DNA binding domain Zalpha. Here we report the solution structure of free Zalpha and map the interaction surface with Z-DNA, confirming roles previously assigned to residues by mutagenesis. Comparison with the crystal structure of the (Zalpha)(2)/Z-DNA complex shows that most Z-DNA contacting residues in free Zalpha are prepositioned to bind Z-DNA, thus minimizing the entropic cost of binding. Comparison with homologous (alpha+beta)helix-turn-helix/B-DNA complexes suggests that binding of Zalpha to B-DNA is disfavored by steric hindrance, but does not eliminate the possibility that related domains may bind to both B- and Z-DNA.


==Disease==
The solution structure of the Zalpha domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA.,Schade M, Turner CJ, Kuhne R, Schmieder P, Lowenhaupt K, Herbert A, Rich A, Oschkinat H Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12465-70. PMID:10535945<ref>PMID:10535945</ref>
Known diseases associated with this structure: Dyschromatosis symmetrica hereditaria OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601059 601059]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1QGP is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1QGP OCA].
</div>
<div class="pdbe-citations 1qgp" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
The solution structure of the Zalpha domain of the human RNA editing enzyme ADAR1 reveals a prepositioned binding surface for Z-DNA., Schade M, Turner CJ, Kuhne R, Schmieder P, Lowenhaupt K, Herbert A, Rich A, Oschkinat H, Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12465-70. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10535945 10535945]
*[[Adenosine deaminase 3D structures|Adenosine deaminase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Herbert, A.]]
[[Category: Herbert A]]
[[Category: Kuehne, R.]]
[[Category: Kuehne R]]
[[Category: Lowenhaupt, K.]]
[[Category: Lowenhaupt K]]
[[Category: Oschkinat, H.]]
[[Category: Oschkinat H]]
[[Category: Rich, A.]]
[[Category: Rich A]]
[[Category: Schade, M.]]
[[Category: Schade M]]
[[Category: Schmieder, P.]]
[[Category: Schmieder P]]
[[Category: Turner, C.J.]]
[[Category: Turner CJ]]
[[Category: adar1]]
[[Category: helix- turn-helix]]
[[Category: rna-editing]]
[[Category: z-alpha-z-dna binding domain]]
[[Category: z-dna recognition]]
 
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Latest revision as of 23:48, 27 December 2023

NMR STRUCTURE OF THE Z-ALPHA DOMAIN OF ADAR1, 15 STRUCTURES

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