2lwe

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[[Image:2lwe.png|left|200px]]
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==Solution structure of mutant (T170E) second CARD of human RIG-I==
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<StructureSection load='2lwe' size='340' side='right' caption='[[2lwe]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2lwe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LWE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LWE FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2lwd|2lwd]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DDX58 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2lwe FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lwe OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lwe RCSB], [http://www.ebi.ac.uk/pdbsum/2lwe PDBsum]</span></td></tr>
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</table>
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== Function ==
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[[http://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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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RIG-I is a cytosolic sensor of viral RNA, comprised of two N-terminal CARDs followed by helicase and C-terminal regulatory domains (helicase-CTD). Viral RNA binds to the helicase-CTD and "exposes" the CARDs for downstream signaling. The role of the second CARD (CARD2) is essential as RIG-I activation requires dephosphorylation of Thr170 followed by ubiquitination at Lys172. Here, we present the solution structure and dynamics of human RIG-I CARD2. Surprisingly, we find that Thr170 is mostly buried. Parallel studies on the phosphomimetic T170E mutant suggest that the loss of function upon Thr170 phosphorylation is likely associated with changes in the CARD1-CARD2 interface that may prevent Lys172 ubiquitination and/or binding to free K63-linked polyubiquitin. We also demonstrate a strong interaction between CARD2 and the helicase-CTD, and show that mutations at the interface result in constitutive activation of RIG-I. Collectively, our data suggests a close interplay between phosphorylation, ubiquitination, and activation of human RIG-I, all mediated by CARD2.
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{{STRUCTURE_2lwe| PDB=2lwe | SCENE= }}
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Structure and Dynamics of the Second CARD of Human RIG-I Provide Mechanistic Insights into Regulation of RIG-I Activation.,Ferrage F, Dutta K, Nistal-Villan E, Patel JR, Sanchez-Aparicio MT, De Ioannes P, Buku A, Aseguinolaza GG, Garcia-Sastre A, Aggarwal AK Structure. 2012 Dec 5;20(12):2048-61. doi: 10.1016/j.str.2012.09.003. Epub 2012, Oct 11. PMID:23063562<ref>PMID:23063562</ref>
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===Solution structure of mutant (T170E) second CARD of human RIG-I===
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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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{{ABSTRACT_PUBMED_23063562}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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[[2lwe]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LWE OCA].
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Aggarwal, A.]]
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[[Category: Aggarwal, A]]
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[[Category: Dutta, K.]]
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[[Category: Dutta, K]]
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[[Category: Ferrage, F.]]
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[[Category: Ferrage, F]]
[[Category: Card]]
[[Category: Card]]
[[Category: Helicase]]
[[Category: Helicase]]

Revision as of 20:44, 25 December 2014

Solution structure of mutant (T170E) second CARD of human RIG-I

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