2rqa

From Proteopedia

(Difference between revisions)

Revision as of 08:14, 12 September 2018

Solution structure of LGP2 CTD

Structural highlights

2rqa is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	DHX58, D11LGP2E, LGP2 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The RIG-I like receptor (RLR) comprises three homologues: RIG-I (retinoic acid-inducible gene I), MDA5 (melanoma differentiation-associated gene 5), and LGP2 (laboratory of genetics and physiology 2). Each RLR senses different viral infections by recognizing replicating viral RNA in the cytoplasm. The RLR contains a conserved C-terminal domain (CTD), which is responsible for the binding specificity to the viral RNAs, including double-stranded RNA (dsRNA) and 5'-triphosphated single-stranded RNA (5'ppp-ssRNA). Here, the solution structures of the MDA5 and LGP2 CTD domains were solved by NMR and compared with those of RIG-I CTD. The CTD domains each have a similar fold and a similar basic surface but there is the distinct structural feature of a RNA binding loop; The LGP2 and RIG-I CTD domains have a large basic surface, one bank of which is formed by the RNA binding loop. MDA5 also has a large basic surface that is extensively flat due to open conformation of the RNA binding loop. The NMR chemical shift perturbation study showed that dsRNA and 5'ppp-ssRNA are bound to the basic surface of LGP2 CTD, whereas dsRNA is bound to the basic surface of MDA5 CTD but much more weakly, indicating that the conformation of the RNA binding loop is responsible for the sensitivity to dsRNA and 5'ppp-ssRNA. Mutation study of the basic surface and the RNA binding loop supports the conclusion from the structure studies. Thus, the CTD is responsible for the binding affinity to the viral RNAs.

Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors.,Takahasi K, Kumeta H, Tsuduki N, Narita R, Shigemoto T, Hirai R, Yoneyama M, Horiuchi M, Ogura K, Fujita T, Inagaki F J Biol Chem. 2009 Jun 26;284(26):17465-74. Epub 2009 Apr 20. PMID:19380577^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K, Foy E, Loo YM, Gale M Jr, Akira S, Yonehara S, Kato A, Fujita T. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J Immunol. 2005 Sep 1;175(5):2851-8. PMID:16116171
↑ Komuro A, Horvath CM. RNA- and virus-independent inhibition of antiviral signaling by RNA helicase LGP2. J Virol. 2006 Dec;80(24):12332-42. Epub 2006 Oct 4. PMID:17020950 doi:http://dx.doi.org/10.1128/JVI.01325-06
↑ Saito T, Hirai R, Loo YM, Owen D, Johnson CL, Sinha SC, Akira S, Fujita T, Gale M Jr. Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):582-7. Epub 2006 Dec 26. PMID:17190814 doi:0606699104
↑ Murali A, Li X, Ranjith-Kumar CT, Bhardwaj K, Holzenburg A, Li P, Kao CC. Structure and function of LGP2, a DEX(D/H) helicase that regulates the innate immunity response. J Biol Chem. 2008 Jun 6;283(23):15825-33. doi: 10.1074/jbc.M800542200. Epub 2008 , Apr 14. PMID:18411269 doi:http://dx.doi.org/10.1074/jbc.M800542200
↑ Bamming D, Horvath CM. Regulation of signal transduction by enzymatically inactive antiviral RNA helicase proteins MDA5, RIG-I, and LGP2. J Biol Chem. 2009 Apr 10;284(15):9700-12. doi: 10.1074/jbc.M807365200. Epub 2009 , Feb 11. PMID:19211564 doi:10.1074/jbc.M807365200
↑ Broquet AH, Hirata Y, McAllister CS, Kagnoff MF. RIG-I/MDA5/MAVS are required to signal a protective IFN response in rotavirus-infected intestinal epithelium. J Immunol. 2011 Feb 1;186(3):1618-26. doi: 10.4049/jimmunol.1002862. Epub 2010, Dec 27. PMID:21187438 doi:http://dx.doi.org/10.4049/jimmunol.1002862
↑ Chopy D, Pothlichet J, Lafage M, Megret F, Fiette L, Si-Tahar M, Lafon M. Ambivalent role of the innate immune response in rabies virus pathogenesis. J Virol. 2011 Jul;85(13):6657-68. doi: 10.1128/JVI.00302-11. Epub 2011 Apr 27. PMID:21525357 doi:http://dx.doi.org/10.1128/JVI.00302-11
↑ Li X, Ranjith-Kumar CT, Brooks MT, Dharmaiah S, Herr AB, Kao C, Li P. The RIG-I-like receptor LGP2 recognizes the termini of double-stranded RNA. J Biol Chem. 2009 May 15;284(20):13881-91. Epub 2009 Mar 11. PMID:19278996 doi:10.1074/jbc.M900818200
↑ Takahasi K, Kumeta H, Tsuduki N, Narita R, Shigemoto T, Hirai R, Yoneyama M, Horiuchi M, Ogura K, Fujita T, Inagaki F. Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors. J Biol Chem. 2009 Jun 26;284(26):17465-74. Epub 2009 Apr 20. PMID:19380577 doi:10.1074/jbc.M109.007179
↑ Pippig DA, Hellmuth JC, Cui S, Kirchhofer A, Lammens K, Lammens A, Schmidt A, Rothenfusser S, Hopfner KP. The regulatory domain of the RIG-I family ATPase LGP2 senses double-stranded RNA. Nucleic Acids Res. 2009 Apr;37(6):2014-25. Epub 2009 Feb 10. PMID:19208642 doi:10.1093/nar/gkp059
↑ Takahasi K, Kumeta H, Tsuduki N, Narita R, Shigemoto T, Hirai R, Yoneyama M, Horiuchi M, Ogura K, Fujita T, Inagaki F. Solution structures of cytosolic RNA sensor MDA5 and LGP2 C-terminal domains: identification of the RNA recognition loop in RIG-I-like receptors. J Biol Chem. 2009 Jun 26;284(26):17465-74. Epub 2009 Apr 20. PMID:19380577 doi:10.1074/jbc.M109.007179

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rqa"

@@ Line 1: / Line 1: @@
 ==Solution structure of LGP2 CTD==
 <StructureSection load='2rqa' size='340' side='right' caption='[[2rqa]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DHX58, D11LGP2E, LGP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<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=2rqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rqa OCA], [http://pdbe.org/2rqa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rqa RCSB], [http://www.ebi.ac.uk/pdbsum/2rqa PDBsum]</span></td></tr>
+<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=2rqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rqa OCA], [http://pdbe.org/2rqa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2rqa RCSB], [http://www.ebi.ac.uk/pdbsum/2rqa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2rqa ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 13: / Line 14: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rq/2rqa_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/rq/2rqa_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 48: / Line 49: @@
 [[Category: Yoneyama, M]]
 [[Category: Atp-binding]]
+[[Category: Coiled coil]]
+[[Category: Cytoplasm]]
 [[Category: Helicase]]
 [[Category: Hydrolase]]
@@ Line 53: / Line 56: @@
 [[Category: Innate immunity]]
 [[Category: Nucleotide-binding]]
+[[Category: Polymorphism]]
 [[Category: Rna binding protein]]
 [[Category: Rna-binding]]

2rqa

From Proteopedia

Revision as of 08:14, 12 September 2018

Solution structure of LGP2 CTD

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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