2w4r

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{{Seed}}
 
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[[Image:2w4r.png|left|200px]]
 
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==Crystal structure of the regulatory domain of human LGP2==
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The line below this paragraph, containing "STRUCTURE_2w4r", creates the "Structure Box" on the page.
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<StructureSection load='2w4r' size='340' side='right'caption='[[2w4r]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2w4r]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2W4R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W4R FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
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<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>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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{{STRUCTURE_2w4r| PDB=2w4r | SCENE= }}
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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=2w4r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w4r OCA], [https://pdbe.org/2w4r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w4r RCSB], [https://www.ebi.ac.uk/pdbsum/2w4r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w4r ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/DHX58_HUMAN DHX58_HUMAN] Acts as a regulator of DDX58/RIG-I and IFIH1/MDA5 mediated antiviral signaling. Cannot initiate antiviral signaling as it lacks the CARD domain required for activating MAVS/IPS1-dependent signaling events. Can have both negative and positive regulatory functions related to DDX58/RIG-I and IFIH1/MDA5 signaling and this role in regulating signaling may be complex and could probably depend on characteristics of the infecting virus or target cells, or both. Its inhibitory action on DDX58/RIG-I signaling may involve the following mechanisms: competition with DDX58/RIG-I for binding to the viral RNA, binding to DDX58/RIG-I and inhibiting its dimerization and interaction with MAVS/IPS1, competing with IKBKE in its binding to MAVS/IPS1 thereby inhibiting activation of interferon regulatory factor 3 (IRF3). Its positive regulatory role may involve unwinding or stripping nucleoproteins of viral RNA thereby facilitating their recognition by DDX58/RIG-I and IFIH1/MDA5. Involved in the innate immune response to various RNA viruses and some DNA viruses such as poxviruses, and also to the bacterial pathogen Listeria monocytogenes. Can bind both ssRNA and dsRNA, with a higher affinity for dsRNA. Shows a preference to 5'-triphosphorylated RNA, although it can recognize RNA lacking a 5'-triphosphate.<ref>PMID:16116171</ref> <ref>PMID:17020950</ref> <ref>PMID:17190814</ref> <ref>PMID:18411269</ref> <ref>PMID:19211564</ref> <ref>PMID:21187438</ref> <ref>PMID:21525357</ref> <ref>PMID:19278996</ref> <ref>PMID:19380577</ref> <ref>PMID:19208642</ref>
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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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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/w4/2w4r_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=2w4r 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 ==
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RIG-I and MDA5 sense cytoplasmic viral RNA and set-off a signal transduction cascade, leading to antiviral innate immune response. The third RIG-I-like receptor, LGP2, differentially regulates RIG-I- and MDA5-dependent RNA sensing in an unknown manner. All three receptors possess a C-terminal regulatory domain (RD), which in the case of RIG-I senses the viral pattern 5'-triphosphate RNA and activates ATP-dependent signaling by RIG-I. Here we report the 2.6 A crystal structure of LGP2 RD along with in vitro and in vivo functional analyses and a homology model of MDA5 RD. Although LGP2 RD is structurally related to RIG-I RD, we find it rather binds double-stranded RNA (dsRNA) and this binding is independent of 5'-triphosphates. We identify conserved and receptor-specific parts of the RNA binding site. Latter are required for specific dsRNA binding by LGP2 RD and could confer pattern selectivity between RIG-I-like receptors. Our data furthermore suggest that LGP2 RD modulates RIG-I-dependent signaling via competition for dsRNA, another pattern sensed by RIG-I, while a fully functional LGP2 is required to augment MDA5-dependent signaling.
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===CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF HUMAN LGP2===
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The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA.,Pippig DA, Hellmuth JC, Cui S, Kirchhofer A, Lammens K, Lammens A, Schmidt A, Rothenfusser S, Hopfner KP Nucleic Acids Res. 2009 Apr;37(6):2014-25. Epub 2009 Feb 10. PMID:19208642<ref>PMID:19208642</ref>
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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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The line below this paragraph, {{ABSTRACT_PUBMED_19208642}}, adds the Publication Abstract to the page
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<div class="pdbe-citations 2w4r" style="background-color:#fffaf0;"></div>
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(as it appears on PubMed at http://www.pubmed.gov), where 19208642 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19208642}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2W4R is a 4 chains structure of sequences 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=2W4R OCA].
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==Reference==
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<ref group="xtra">PMID:19208642</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Cui, S.]]
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[[Category: Large Structures]]
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[[Category: Hellmuth, J C.]]
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[[Category: Cui S]]
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[[Category: Hopfner, K P.]]
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[[Category: Hellmuth JC]]
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[[Category: Kirchhofer, A.]]
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[[Category: Hopfner KP]]
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[[Category: Lammens, A.]]
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[[Category: Kirchhofer A]]
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[[Category: Lammens, K.]]
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[[Category: Lammens A]]
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[[Category: Pippig, D A.]]
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[[Category: Lammens K]]
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[[Category: Rothenfusser, S.]]
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[[Category: Pippig DA]]
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[[Category: Schmidt, A.]]
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[[Category: Rothenfusser S]]
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[[Category: Atp-binding]]
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[[Category: Schmidt A]]
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[[Category: Coiled coil]]
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[[Category: Cytoplasm]]
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[[Category: Double-strand rna binding protein]]
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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: Nucleotide-binding]]
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[[Category: Polymorphism]]
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[[Category: Rna-binding]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 15 09:10:02 2009''
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Current revision

Crystal structure of the regulatory domain of human LGP2

PDB ID 2w4r

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