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| | ==The complex crystal structure of the DNA binding domain of vIRF-1 from the oncogenic KSHV with DNA== | | ==The complex crystal structure of the DNA binding domain of vIRF-1 from the oncogenic KSHV with DNA== |
| - | <StructureSection load='4hly' size='340' side='right' caption='[[4hly]], [[Resolution|resolution]] 1.48Å' scene=''> | + | <StructureSection load='4hly' size='340' side='right'caption='[[4hly]], [[Resolution|resolution]] 1.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hly]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-8 Hhv-8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HLY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HLY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hly]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_gammaherpesvirus_8 Human gammaherpesvirus 8] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HLY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HLY FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF K9, vIRF, vIRF-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=37296 HHV-8])</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]] 1.48Å</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=4hly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hly OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hly RCSB], [http://www.ebi.ac.uk/pdbsum/4hly PDBsum]</span></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=4hly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hly OCA], [https://pdbe.org/4hly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hly RCSB], [https://www.ebi.ac.uk/pdbsum/4hly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hly ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/VIRF1_HHV8P VIRF1_HHV8P] Plays a role in the inhibition of host innate response by repressing the expression of interferon-inducible genes and blocking host IRF1- and IRF3-mediated transcription. Blocks the interaction between host IRF3 and CREBBP. Regulates the host cellular metabolism by increasing glucose uptake, ATP production and lactate secretion through down-regulation of heterogeneous nuclear ribonuclear protein Q1/SYNCRIP. Mechanistically, induces ubiquitination and degradation of SYNCRIP through the ubiquitin-proteasome pathway by recruiting KLHL3/CUL3 ubiquitin ligase complex (PubMed:35538151). Disrupts host TP53 signaling pathway during viral infection by interacting with host USP7 and thereby decreasing the availability of USP7 for deubiquitinating and stabilizing TP53 (PubMed:26786098).<ref>PMID:11314014</ref> <ref>PMID:26786098</ref> <ref>PMID:35538151</ref> <ref>PMID:9365244</ref> <ref>PMID:9420276</ref> |
| - | Kaposi's sarcoma-associated herpesvirus encodes four viral homologues to cellular interferon regulatory factors (IRFs), where the most studied is vIRF-1. Even though vIRF-1 shows sequence homology to the N-terminal DNA-binding domain (DBD) of human IRFs, a specific role for this domain in vIRF-1's function has remained uncertain. To provide insights into the function of the vIRF-1 DBD, we have determined the crystal structure of it in complex with DNA and in its apo-form. Using a thermal stability shift assay (TSSA), we show that the vIRF-1 DBD binds DNA, whereas full-length vIRF-1 does not, suggesting a cis-acting regulatory mechanism in similarity to human IRFs. The complex structure of vIRF-1 DBD reveals interactions with the DNA backbone and the positioning of two arginines for specific recognition in the major grove. A superimposition with human IRF-3 reveals a similar positioning of the two specificity-determining arginines, and additional TSSAs indicate binding of vIRF-1 to an IRF-3 operator consensus sequence. The results from this study, therefore, provide support that vIRF-1 has evolved to bind DNA and plays a role in DNA binding in the context of transcriptional regulation and might act on some of the many operator sequences controlled by human IRF-3.
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| - | The crystal structure of the DNA-binding domain of vIRF-1 from the oncogenic KSHV reveals a conserved fold for DNA binding and reinforces its role as a transcription factor.,Hew K, Dahlroth SL, Venkatachalam R, Nasertorabi F, Lim BT, Cornvik T, Nordlund P Nucleic Acids Res. 2013 Feb 21. PMID:23435230<ref>PMID:23435230</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | ==See Also== |
| - | </div>
| + | *[[Interferon regulatory factor|Interferon regulatory factor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hhv-8]] | + | [[Category: Human gammaherpesvirus 8]] |
| - | [[Category: Hew, K]] | + | [[Category: Large Structures]] |
| - | [[Category: Venkatachalam, R]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Dna binding protein-dna complex]] | + | [[Category: Hew K]] |
| - | [[Category: Helix-turn-helix]] | + | [[Category: Venkatachalam R]] |
| Structural highlights
Function
VIRF1_HHV8P Plays a role in the inhibition of host innate response by repressing the expression of interferon-inducible genes and blocking host IRF1- and IRF3-mediated transcription. Blocks the interaction between host IRF3 and CREBBP. Regulates the host cellular metabolism by increasing glucose uptake, ATP production and lactate secretion through down-regulation of heterogeneous nuclear ribonuclear protein Q1/SYNCRIP. Mechanistically, induces ubiquitination and degradation of SYNCRIP through the ubiquitin-proteasome pathway by recruiting KLHL3/CUL3 ubiquitin ligase complex (PubMed:35538151). Disrupts host TP53 signaling pathway during viral infection by interacting with host USP7 and thereby decreasing the availability of USP7 for deubiquitinating and stabilizing TP53 (PubMed:26786098).[1] [2] [3] [4] [5]
See Also
References
- ↑ Lin R, Genin P, Mamane Y, Sgarbanti M, Battistini A, Harrington WJ Jr, Barber GN, Hiscott J. HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators. Oncogene. 2001 Feb 15;20(7):800-11. doi: 10.1038/sj.onc.1204163. PMID:11314014 doi:http://dx.doi.org/10.1038/sj.onc.1204163
- ↑ Chavoshi S, Egorova O, Lacdao IK, Farhadi S, Sheng Y, Saridakis V. Identification of Kaposi Sarcoma Herpesvirus (KSHV) vIRF1 Protein as a Novel Interaction Partner of Human Deubiquitinase USP7. J Biol Chem. 2016 Mar 18;291(12):6281-91. doi: 10.1074/jbc.M115.710632. Epub 2016, Jan 19. PMID:26786098 doi:http://dx.doi.org/10.1074/jbc.M115.710632
- ↑ Qi X, Yan Q, Shang Y, Zhao R, Ding X, Gao SJ, Li W, Lu C. A viral interferon regulatory factor degrades RNA-binding protein hnRNP Q1 to enhance aerobic glycolysis via recruiting E3 ubiquitin ligase KLHL3 and decaying GDPD1 mRNA. Cell Death Differ. 2022 Nov;29(11):2233-2246. doi: 10.1038/s41418-022-01011-1., Epub 2022 May 10. PMID:35538151 doi:http://dx.doi.org/10.1038/s41418-022-01011-1
- ↑ Gao SJ, Boshoff C, Jayachandra S, Weiss RA, Chang Y, Moore PS. KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene. 1997 Oct 16;15(16):1979-85. doi: 10.1038/sj.onc.1201571. PMID:9365244 doi:http://dx.doi.org/10.1038/sj.onc.1201571
- ↑ Zimring JC, Goodbourn S, Offermann MK. Human herpesvirus 8 encodes an interferon regulatory factor (IRF) homolog that represses IRF-1-mediated transcription. J Virol. 1998 Jan;72(1):701-7. doi: 10.1128/JVI.72.1.701-707.1998. PMID:9420276 doi:http://dx.doi.org/10.1128/JVI.72.1.701-707.1998
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