4hly
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<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> | <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='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> | + | </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'>[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> | ||
== Function == | == Function == | ||
[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> | [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> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4hly" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
The complex crystal structure of the DNA binding domain of vIRF-1 from the oncogenic KSHV with DNA
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