Identification of Herpes TATT-binding protein

doi:10.1016/j.antiviral.2007.03.002

Antiviral Research

Volume 75, Issue 2, August 2007, Pages 167-172

https://doi.org/10.1016/j.antiviral.2007.03.002 Get rights and content

Abstract

The regulation of viral gene expression is a compilation of virus and host factors influencing the transcription machinery. In Epstein-Barr Virus (EBV) a distinct regulatory element utilizing the TATT-box was described. The motif is present in promoters of lytic cycle genes and resembles a crucial host genome motif (TATA-box). Since the binding specificity of eukaryotic proteins recognizing TATA-box (TBP) was determined and no specific preference for interaction with TATT motif was found, we performed a genome-wide fold recognition search to identify viral proteins potentially recognizing the TATT-box. By applying profile–profile comparisons and homology-based protein structure prediction we identified a protein of unknown function from Gammaherpesvirinae (BcRF1 of EBV) and their Betaherpesvirinae homologs (UL87 of CMV) as proteins encoding TBP fold. Although overall sequence identity is very low (circa 10%), the saddle-like fold and presence of important residues on a surface of DNA–protein interface marked both proteins as distantly related to TBP and permitted the characterization of a putative molecular basis of selective recognition of TATT-motif by BcRF1.

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Acknowledgements

This work has been supported by MNiSW and the European Commission (LSHG-CT-2003-503265, LSHG-CT-2004-512035) and MNiSW (2P05A00130 and PBZ-MNiI-2/1/2005). LSW is a fellow of the Young Scientist Award from The Foundation for Polish Science. Authors would like to thank Dariusz Plewczynski for support in molecular dynamics calculations and Grzegorz Koczyk for critical reading of the manuscript.

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Citation Excerpt :
A major breakthrough came in 2012, when the Manet group showed that the EBV homolog BcRF1 is required for late gene transcription. They showed that purified BcRF1 protein is capable of binding to a late gene promoter in vitro and is dependent on the aforementioned asparagine residues predicted to be important for DNA binding in TBP [10,69]. KSHV and MHV68 ORF24 were also found to be able to bind to TATT-containing DNA probes in vitro [9,57].
During lytic replication, herpesviruses express their genes in a temporal cascade culminating in expression of “late” genes. Two subfamilies of herpesviruses, the beta- and gammaherpesviruses (including human herpesviruses cytomegalovirus, Epstein-Barr virus, and Kaposi’s sarcoma-associated herpesvirus), use a unique strategy to facilitate transcription of late genes. They encode six essential viral transcriptional activators (vTAs) that form a complex at a subset of late gene promoters. One of these vTAs is a viral mimic of host TATA-binding protein (vTBP) that recognizes a strikingly minimal cis-acting element consisting of a modified TATA box with a TATTWAA consensus sequence. vTBP is also responsible for recruitment of cellular RNA polymerase II (Pol II). Despite extensive work in the beta/gammaherpesviruses, the function of the other five vTAs remains largely unknown. The vTA complex and Pol II assemble on the promoter into a viral preinitiation complex (vPIC) to facilitate late gene transcription. Here, we review the properties of the vTAs and the promoters on which they act.
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A genome-wide interaction study of KSHV identified ORF24 to be the essential DNA binding protein of the vPIC, which subsequently recruited the other 5 complex members (Davis et al., 2015). The EBV and HCMV orthologs of ORF24, BcRF1, and UL87, respectively, share the conserved TBP fold, so are likely to be the DNA binding proteins in their respective vPICs (Gruffat et al., 2012; Wyrwicz and Rychlewski, 2007). KSHV ORF24 has also been shown to recruit host RNA polymerase, based on conserved residues in the N-terminal domain binding to both the C-terminal domain of host pol II and promoter DNA (Castañeda et al., 2020).
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Short communicationIdentification of Herpes TATT-binding protein

Abstract

Section snippets

Acknowledgements

J. Mol. Biol.

J. Mol. Biol.

The Protein Data Bank

Nucleic Acids Res.

Minor groove-binding architectural proteins: structure, function, and DNA recognition

Annu. Rev. Biophys. Biomol. Struct.

Structure prediction meta server

Bioinformatics

3D-SHOTGUN: a novel, cooperative, fold-recognition meta-predictor

Proteins

3D-Jury: a simple approach to improve protein structure predictions

Bioinformatics

ORFeus: detection of distant homology using sequence profiles and predicted secondary structure

Nucleic Acids Res.

Short communication
Identification of Herpes TATT-binding protein