8gbd
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Homo sapiens Zalpha mutant - P193A== | |
| + | <StructureSection load='8gbd' size='340' side='right'caption='[[8gbd]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8gbd]] 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=8GBD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GBD FirstGlance]. <br> | ||
| + | </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=8gbd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gbd OCA], [https://pdbe.org/8gbd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gbd RCSB], [https://www.ebi.ac.uk/pdbsum/8gbd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gbd 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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The Zalpha domain of ADARp150 is critical for proper Z-RNA substrate binding and is a key factor in the type-I interferon response pathway. Two point-mutations in this domain (N173S and P193A), which cause neurodegenerative disorders, are linked to decreased A-to-I editing in disease models. To understand this phenomenon at the molecular level, we biophysically and structurally characterized these two mutated domains, revealing that they bind Z-RNA with a decreased affinity. Less efficient binding to Z-RNA can be explained by structural changes in beta-wing, part of the Z-RNA-protein interface, and alteration of conformational dynamics of the proteins. | ||
| - | + | Differential Structural Features of Two Mutant ADAR1p150 Zalpha Domains Associated with Aicardi-Goutieres Syndrome.,Langeberg CJ, Nichols PJ, Henen MA, Vicens Q, Vogeli B J Mol Biol. 2023 Mar 7;435(8):168040. doi: 10.1016/j.jmb.2023.168040. PMID:36889460<ref>PMID:36889460</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8gbd" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Henen M]] | ||
| + | [[Category: Langeberg CJ]] | ||
| + | [[Category: Nichols PJ]] | ||
| + | [[Category: Vicens Q]] | ||
| + | [[Category: Vogeli B]] | ||
Current revision
Homo sapiens Zalpha mutant - P193A
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