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2qfd

From Proteopedia

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[[Image:2qfd.jpg|left|200px]]
 
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{{Structure
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==Crystal structure of the regulatory domain of human RIG-I with bound Hg==
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|PDB= 2qfd |SIZE=350|CAPTION= <scene name='initialview01'>2qfd</scene>, resolution 2.7&Aring;
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<StructureSection load='2qfd' size='340' side='right'caption='[[2qfd]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Hg+Binding+Site+For+Residue+A+1001'>AC1</scene>, <scene name='pdbsite=AC2:Hg+Binding+Site+For+Residue+B+1002'>AC2</scene>, <scene name='pdbsite=AC3:Hg+Binding+Site+For+Residue+C+1003'>AC3</scene>, <scene name='pdbsite=AC4:Hg+Binding+Site+For+Residue+D+1004'>AC4</scene>, <scene name='pdbsite=AC5:Hg+Binding+Site+For+Residue+E+1005'>AC5</scene>, <scene name='pdbsite=AC6:Hg+Binding+Site+For+Residue+F+1006'>AC6</scene>, <scene name='pdbsite=AC7:Hg+Binding+Site+For+Residue+G+1007'>AC7</scene>, <scene name='pdbsite=AC8:Hg+Binding+Site+For+Residue+H+1008'>AC8</scene>, <scene name='pdbsite=AC9:Hg+Binding+Site+For+Residue+I+1009'>AC9</scene> and <scene name='pdbsite=BC1:Hg+Binding+Site+For+Residue+J+1010'>BC1</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene>
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<table><tr><td colspan='2'>[[2qfd]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QFD FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HG:MERCURY+(II)+ION'>HG</scene></td></tr>
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|GENE= DDX58 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qfb|2qfb]]</div></td></tr>
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|DOMAIN=
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDX58 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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|RELATEDENTRY=[[2qfb|2QFB]]
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qfd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qfd OCA], [https://pdbe.org/2qfd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qfd RCSB], [https://www.ebi.ac.uk/pdbsum/2qfd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qfd ProSAT]</span></td></tr>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qfd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qfd OCA], [http://www.ebi.ac.uk/pdbsum/2qfd PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qfd RCSB]</span>
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</table>
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}}
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== Function ==
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[[https://www.uniprot.org/uniprot/DDX58_HUMAN DDX58_HUMAN]] Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects rotavirus and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration.<ref>PMID:15208624</ref> <ref>PMID:16125763</ref> <ref>PMID:15708988</ref> <ref>PMID:16153868</ref> <ref>PMID:16127453</ref> <ref>PMID:17190814</ref> <ref>PMID:18636086</ref> <ref>PMID:19631370</ref> <ref>PMID:19576794</ref> <ref>PMID:19122199</ref> <ref>PMID:19211564</ref> <ref>PMID:19609254</ref> <ref>PMID:21742966</ref>
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'''Crystal structure of the regulatory domain of human RIG-I with bound Hg'''
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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==Overview==
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qf/2qfd_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2qfd ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
The ATPase RIG-I senses viral RNAs that contain 5'-triphosphates in the cytoplasm. It initiates a signaling cascade that activates innate immune response by interferon and cytokine production, providing essential antiviral protection for the host. The mode of RNA 5'-triphosphate sensing by RIG-I remains elusive. We show that the C-terminal regulatory domain RD of RIG-I binds viral RNA in a 5'-triphosphate-dependent manner and activates the RIG-I ATPase by RNA-dependent dimerization. The crystal structure of RD reveals a zinc-binding domain that is structurally related to GDP/GTP exchange factors of Rab-like GTPases. The zinc coordination site is essential for RIG-I signaling and is also conserved in MDA5 and LGP2, suggesting related RD domains in all three enzymes. Structure-guided mutagenesis identifies a positively charged groove as likely 5'-triphosphate-binding site of RIG-I. This groove is distinct in MDA5 and LGP2, raising the possibility that RD confers ligand specificity.
The ATPase RIG-I senses viral RNAs that contain 5'-triphosphates in the cytoplasm. It initiates a signaling cascade that activates innate immune response by interferon and cytokine production, providing essential antiviral protection for the host. The mode of RNA 5'-triphosphate sensing by RIG-I remains elusive. We show that the C-terminal regulatory domain RD of RIG-I binds viral RNA in a 5'-triphosphate-dependent manner and activates the RIG-I ATPase by RNA-dependent dimerization. The crystal structure of RD reveals a zinc-binding domain that is structurally related to GDP/GTP exchange factors of Rab-like GTPases. The zinc coordination site is essential for RIG-I signaling and is also conserved in MDA5 and LGP2, suggesting related RD domains in all three enzymes. Structure-guided mutagenesis identifies a positively charged groove as likely 5'-triphosphate-binding site of RIG-I. This groove is distinct in MDA5 and LGP2, raising the possibility that RD confers ligand specificity.
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==About this Structure==
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The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I.,Cui S, Eisenacher K, Kirchhofer A, Brzozka K, Lammens A, Lammens K, Fujita T, Conzelmann KK, Krug A, Hopfner KP Mol Cell. 2008 Feb 1;29(2):169-79. PMID:18243112<ref>PMID:18243112</ref>
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2QFD is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QFD OCA].
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==Reference==
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The C-Terminal Regulatory Domain Is the RNA 5'-Triphosphate Sensor of RIG-I., Cui S, Eisenacher K, Kirchhofer A, Brzozka K, Lammens A, Lammens K, Fujita T, Conzelmann KK, Krug A, Hopfner KP, Mol Cell. 2008 Feb 1;29(2):169-179. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18243112 18243112]
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[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Cui, S.]]
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[[Category: Hopfner, K P.]]
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[[Category: Lammens, A.]]
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[[Category: Lammens, K.]]
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[[Category: alternative splicing]]
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[[Category: antiviral defense]]
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[[Category: atp-binding]]
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[[Category: helicase]]
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[[Category: hydrolase]]
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[[Category: immune response]]
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[[Category: innate immunity]]
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[[Category: interferon induction]]
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[[Category: nucleotide-binding]]
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[[Category: polymorphism]]
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[[Category: rna-binding]]
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[[Category: ubl conjugation]]
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[[Category: zinc finger]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:48:42 2008''
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2qfd" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Human]]
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[[Category: Large Structures]]
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[[Category: Cui, S]]
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[[Category: Hopfner, K P]]
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[[Category: Lammens, A]]
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[[Category: Lammens, K]]
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[[Category: Alternative splicing]]
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[[Category: Antiviral defense]]
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[[Category: Atp-binding]]
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[[Category: Helicase]]
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[[Category: Hydrolase]]
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[[Category: Immune response]]
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[[Category: Innate immunity]]
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[[Category: Interferon induction]]
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[[Category: Nucleotide-binding]]
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[[Category: Polymorphism]]
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[[Category: Rna-binding]]
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[[Category: Ubl conjugation]]
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[[Category: Zinc finger]]

Current revision

Crystal structure of the regulatory domain of human RIG-I with bound Hg

PDB ID 2qfd

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