2mdr
From Proteopedia
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| - | ''' | + | ==Solution structure of the third double-stranded RNA-binding domain (dsRBD3) of human adenosine-deaminase ADAR1== |
| + | <StructureSection load='2mdr' size='340' side='right' caption='[[2mdr]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | [[2mdr]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MDR OCA]. <br> | ||
| + | <b>Activity:</b> <span class='plainlinks'>[http://en.wikipedia.org/wiki/Glucokinase Glucokinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.2 2.7.1.2] </span><br> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/DSRAD_HUMAN DSRAD_HUMAN]] Defects in ADAR are a cause of dyschromatosis symmetrical hereditaria (DSH) [MIM:[http://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 == | ||
| + | [[http://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> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The human RNA-editing enzyme adenosine deaminase acting on RNA (ADAR1) carries a unique nuclear localization signal (NLS) that overlaps one of its double-stranded RNA-binding domains (dsRBDs). This dsRBD-NLS is recognized by the nuclear import receptor transportin 1 (Trn1; also called karyopherin-beta2) in an RNA-sensitive manner. Most Trn1 cargos bear a well-characterized proline-tyrosine-NLS, which is missing from the dsRBD-NLS. Here, we report the structure of the dsRBD-NLS, which reveals an unusual dsRBD fold extended by an additional N-terminal alpha-helix that brings the N- and C-terminal flanking regions in close proximity. We demonstrate experimentally that the atypical ADAR1-NLS is bimodular and is formed by the combination of the two flexible fragments flanking the folded domain. The intervening dsRBD acts only as an RNA-sensing scaffold, allowing the two NLS modules to be properly positioned for interacting with Trn1. We also provide a structural model showing how Trn1 can recognize the dsRBD-NLS and how dsRNA binding can interfere with Trn1 binding. | ||
| - | + | A bimodular nuclear localization signal assembled via an extended double-stranded RNA-binding domain acts as an RNA-sensing signal for transportin 1.,Barraud P, Banerjee S, Mohamed WI, Jantsch MF, Allain FH Proc Natl Acad Sci U S A. 2014 Apr 21. PMID:24753571<ref>PMID:24753571</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | == References == | |
| - | + | <references/> | |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Double-stranded RNA adenine deaminase]] | ||
| + | [[Category: Allain, F H.]] | ||
| + | [[Category: Banerjee, S.]] | ||
| + | [[Category: Barraud, P.]] | ||
| + | [[Category: Jantsch, M F.]] | ||
| + | [[Category: Mohamed, W I.]] | ||
| + | [[Category: Deaminase]] | ||
| + | [[Category: Hydrolase]] | ||
Revision as of 07:46, 30 April 2014
Solution structure of the third double-stranded RNA-binding domain (dsRBD3) of human adenosine-deaminase ADAR1
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