| Structural highlights
Function
ICP4_HHV11 Plays an essential role in the regulation of viral gene expression by both activating and repressing host RNA polymerase II-mediated transcription. Binds with high affinity to the sequence 5'-ATCGTC-3'. Activates transcription by recruiting a form of the host TFIID to promoters and stabilizing the pre-initiation complex formation. Negatively regulates its own transcription. This immediate early (IE) protein is absolutely necessary for the transition from IE transcription to later viral gene transcription.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
The transcription factor ICP4 from herpes simplex virus has a central role in regulating the gene expression cascade which controls viral infection. Here we present the crystal structure of the functionally essential ICP4 DNA binding domain in complex with a segment from its own promoter, revealing a novel homo-dimeric fold. We also studied the complex in solution by small angle X-Ray scattering, nuclear magnetic resonance and surface-plasmon resonance which indicated that, in addition to the globular domain, a flanking intrinsically disordered region also recognizes DNA. Together the data provides a rationale for the bi-partite nature of the ICP4 DNA recognition consensus sequence as the globular and disordered regions bind synergistically to adjacent DNA motifs. Therefore in common with its eukaryotic host, the viral transcription factor ICP4 utilizes disordered regions to enhance the affinity and tune the specificity of DNA interactions in tandem with a globular domain.
The herpes viral transcription factor ICP4 forms a novel DNA recognition complex.,Tunnicliffe RB, Lockhart-Cairns MP, Levy C, Mould AP, Jowitt TA, Sito H, Baldock C, Sandri-Goldin RM, Golovanov AP Nucleic Acids Res. 2017 May 13. doi: 10.1093/nar/gkx419. PMID:28505309[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sampath P, Deluca NA. Binding of ICP4, TATA-binding protein, and RNA polymerase II to herpes simplex virus type 1 immediate-early, early, and late promoters in virus-infected cells. J Virol. 2008 Mar;82(5):2339-49. Epub 2007 Dec 19. PMID:18094162 doi:http://dx.doi.org/10.1128/JVI.02459-07
- ↑ Zabierowski SE, Deluca NA. Stabilized binding of TBP to the TATA box of herpes simplex virus type 1 early (tk) and late (gC) promoters by TFIIA and ICP4. J Virol. 2008 Apr;82(7):3546-54. doi: 10.1128/JVI.02560-07. Epub 2008 Jan 23. PMID:18216093 doi:http://dx.doi.org/10.1128/JVI.02560-07
- ↑ Papavassiliou AG, Wilcox KW, Silverstein SJ. The interaction of ICP4 with cell/infected-cell factors and its state of phosphorylation modulate differential recognition of leader sequences in herpes simplex virus DNA. EMBO J. 1991 Feb;10(2):397-406. PMID:1846804
- ↑ Wagner LM, Lester JT, Sivrich FL, DeLuca NA. The N terminus and C terminus of herpes simplex virus 1 ICP4 cooperate to activate viral gene expression. J Virol. 2012 Jun;86(12):6862-74. doi: 10.1128/JVI.00651-12. Epub 2012 Apr 11. PMID:22496239 doi:http://dx.doi.org/10.1128/JVI.00651-12
- ↑ Wagner LM, Bayer A, Deluca NA. Requirement of the N-terminal activation domain of herpes simplex virus ICP4 for viral gene expression. J Virol. 2013 Jan;87(2):1010-8. doi: 10.1128/JVI.02844-12. Epub 2012 Nov 7. PMID:23135715 doi:http://dx.doi.org/10.1128/JVI.02844-12
- ↑ Wagner LM, DeLuca NA. Temporal association of herpes simplex virus ICP4 with cellular complexes functioning at multiple steps in PolII transcription. PLoS One. 2013 Oct 11;8(10):e78242. doi: 10.1371/journal.pone.0078242., eCollection 2013. PMID:24147125 doi:http://dx.doi.org/10.1371/journal.pone.0078242
- ↑ Carrozza MJ, DeLuca NA. Interaction of the viral activator protein ICP4 with TFIID through TAF250. Mol Cell Biol. 1996 Jun;16(6):3085-93. PMID:8649420
- ↑ Tunnicliffe RB, Lockhart-Cairns MP, Levy C, Mould AP, Jowitt TA, Sito H, Baldock C, Sandri-Goldin RM, Golovanov AP. The herpes viral transcription factor ICP4 forms a novel DNA recognition complex. Nucleic Acids Res. 2017 May 13. doi: 10.1093/nar/gkx419. PMID:28505309 doi:http://dx.doi.org/10.1093/nar/gkx419
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