4hly

The complex crystal structure of the DNA binding domain of vIRF-1 from the oncogenic KSHV with DNAThe complex crystal structure of the DNA binding domain of vIRF-1 from the oncogenic KSHV with DNA

Structural highlights

4hly is a 4 chain structure with sequence from Human gammaherpesvirus 8 and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.48Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

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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OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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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