5jer

From Proteopedia

(Difference between revisions)

Revision as of 11:01, 6 September 2023

Structure of Rotavirus NSP1 bound to IRF-3

Structural highlights

5jer is a 8 chain structure with sequence from Homo sapiens and Rotavirus A. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.913Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NSP1_ROTS4 Plays a role in the inhibition of host innate immunity by inducing the degradation of key host factors required to activate interferon production such as IRF3, IRF5 or IRF7. Associates with components of cullin RING ligases (CRLs) including CUL1 or CUL3, which are essential multisubunit ubiquitination complexes, to modulate their activities.[HAMAP-Rule:MF_04088]^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Type I IFNs are key cytokines mediating innate antiviral immunity. cGMP-AMP synthase, ritinoic acid-inducible protein 1 (RIG-I)-like receptors, and Toll-like receptors recognize microbial double-stranded (ds)DNA, dsRNA, and LPS to induce the expression of type I IFNs. These signaling pathways converge at the recruitment and activation of the transcription factor IRF-3 (IFN regulatory factor 3). The adaptor proteins STING (stimulator of IFN genes), MAVS (mitochondrial antiviral signaling), and TRIF (TIR domain-containing adaptor inducing IFN-beta) mediate the recruitment of IRF-3 through a conserved pLxIS motif. Here we show that the pLxIS motif of phosphorylated STING, MAVS, and TRIF binds to IRF-3 in a similar manner, whereas residues upstream of the motif confer specificity. The structure of the IRF-3 phosphomimetic mutant S386/396E bound to the cAMP response element binding protein (CREB)-binding protein reveals that the pLxIS motif also mediates IRF-3 dimerization and activation. Moreover, rotavirus NSP1 (nonstructural protein 1) employs a pLxIS motif to target IRF-3 for degradation, but phosphorylation of NSP1 is not required for its activity. These results suggest a concerted mechanism for the recruitment and activation of IRF-3 that can be subverted by viral proteins to evade innate immune responses.

Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins.,Zhao B, Shu C, Gao X, Sankaran B, Du F, Shelton CL, Herr AB, Ji JY, Li P Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3403-12. doi:, 10.1073/pnas.1603269113. Epub 2016 Jun 2. PMID:27302953^[6]

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

References

↑ Barro M, Patton JT. Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3. Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):4114-9. PMID:15741273 doi:10.1073/pnas.0408376102
↑ Graff JW, Ewen J, Ettayebi K, Hardy ME. Zinc-binding domain of rotavirus NSP1 is required for proteasome-dependent degradation of IRF3 and autoregulatory NSP1 stability. J Gen Virol. 2007 Feb;88(Pt 2):613-620. PMID:17251580 doi:10.1099/vir.0.82255-0
↑ Barro M, Patton JT. Rotavirus NSP1 inhibits expression of type I interferon by antagonizing the function of interferon regulatory factors IRF3, IRF5, and IRF7. J Virol. 2007 May;81(9):4473-81. PMID:17301153 doi:10.1128/JVI.02498-06
↑ Lutz LM, Pace CR, Arnold MM. Rotavirus NSP1 Associates with Components of the Cullin RING Ligase Family of E3 Ubiquitin Ligases. J Virol. 2016 Jun 10;90(13):6036-48. PMID:27099313 doi:10.1128/JVI.00704-16
↑ Zhao B, Shu C, Gao X, Sankaran B, Du F, Shelton CL, Herr AB, Ji JY, Li P. Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins. Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3403-12. doi:, 10.1073/pnas.1603269113. Epub 2016 Jun 2. PMID:27302953 doi:http://dx.doi.org/10.1073/pnas.1603269113
↑ Zhao B, Shu C, Gao X, Sankaran B, Du F, Shelton CL, Herr AB, Ji JY, Li P. Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins. Proc Natl Acad Sci U S A. 2016 Jun 14;113(24):E3403-12. doi:, 10.1073/pnas.1603269113. Epub 2016 Jun 2. PMID:27302953 doi:http://dx.doi.org/10.1073/pnas.1603269113

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jer"

Categories: Homo sapiens | Large Structures | Rotavirus A | Li P | Zhao B

@@ Line 3: / Line 3: @@
 <StructureSection load='5jer' size='340' side='right'caption='[[5jer]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5jer]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Group_a_rotaviruses Group a rotaviruses] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JER OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JER FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5jer]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rotavirus_A Rotavirus A]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JER FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jej|5jej]], [[5jel|5jel]], [[5jek|5jek]], [[5jem|5jem]], [[5jeo|5jeo]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.913&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IRF3 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5jer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jer OCA], [https://pdbe.org/5jer PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jer RCSB], [https://www.ebi.ac.uk/pdbsum/5jer PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jer ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jer OCA], [http://pdbe.org/5jer PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jer RCSB], [http://www.ebi.ac.uk/pdbsum/5jer PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jer ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/IRF3_HUMAN IRF3_HUMAN]] Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages.
+[https://www.uniprot.org/uniprot/NSP1_ROTS4 NSP1_ROTS4] Plays a role in the inhibition of host innate immunity by inducing the degradation of key host factors required to activate interferon production such as IRF3, IRF5 or IRF7. Associates with components of cullin RING ligases (CRLs) including CUL1 or CUL3, which are essential multisubunit ubiquitination complexes, to modulate their activities.[HAMAP-Rule:MF_04088]<ref>PMID:15741273</ref> <ref>PMID:17251580</ref> <ref>PMID:17301153</ref> <ref>PMID:27099313</ref> <ref>PMID:27302953</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Group a rotaviruses]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Li, P]]
+[[Category: Rotavirus A]]
-[[Category: Zhao, B]]
+[[Category: Li P]]
-[[Category: Immune system]]
+[[Category: Zhao B]]
-[[Category: Viral immunity]]

5jer

From Proteopedia

Revision as of 11:01, 6 September 2023

Structure of Rotavirus NSP1 bound to IRF-3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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