Fold recognition insights into function of herpes ICP4 protein
Languages of publication
ICP4 is an important factor regulating the life cycle of HSV1. This conserved protein has several molecular functions, including activation of expression of viral late gene transcripts and inhibition of immediate early genes. Although ICP4 and its Alphaherpesvirinae homologs (eg.: IE62 of VZV) have been subjects of various molecular studies, a complete view of their molecular function is lacking. Here we present the results of fold recognition and molecular modelling of ICP4 functional domains. The performed state-of-the-art bioinformatic fold recognition analysis identified a dual helix-turn-helix motif as a binding module of repressor activities (so called region 2 domain). The mapping of distant homology identified that a segment responsible for activation of late gene promoters (region 4) exhibits folding of uracil DNA glycosylase (UDG), but seems to be a non-functional homolog of UDG. Potential implications of the results are discussed.
- Aravind L, Anantharaman V, Balaji S, Babu MM, Iyer LM (2005) The many faces of the helix-turn-helix domain: transcription regulation and beyond. FEMS Microbiol Rev 29: 231-262.
- Batchelor AH, Wilcox KW, O'Hare P (1994) Binding and repression of the latency-associated promoter of herpes simplex virus by the immediate early 175K protein. J Gen Virol 75: 753-767.
- Beard P Faber S, Wilcox KW, Pizer LI (1986) Herpes simplex virus immediate early infected-cell polypeptide 4 binds to DNA and promotes transcription. Proc Natl Acad Sci USA 83: 4016-4020.
- Bruce JW, Wilcox KW (2002) Identification of a motif in the c terminus of herpes simplex virus regulatory protein ICP4 that contributes to activation of transcription. J Virol 76: 195-207.
- Bujnicki J, Elofsson A, Fischer D, Rychlewski L (2001) Structure prediction meta server. Bioinformatics 17: 750-751.
- Carrozza MJ, DeLuca NA (1996) Interaction of the viral activator protein ICP4 with TFIID through TAF250. Mol Cell Biol 16: 3085-3093.
- DeLuca N, Schaffer P (1988) Physical and functional domains of the herpes simplex virus transcriptional regulatory protein ICP4. J Virol 62: 732-743.
- DiDonato J, Muller M (1989) DNA binding and gene regulation by the herpes simplex virus type 1 protein ICP4 and involvement of the TATA element. J Virol 63: 3737-3747.
- Ekonomiuk D, Kielbasinski M, Kolinski A (2005) Protein modeling with reduced representation: statistical potentials and protein folding mechanism. Acta Biochim Polon 52: 741-748.
- Everett R, DiDonato J, Elliott M, Muller M (1992) Herpes simplex virus type 1 polypeptide ICP4 bends DNA. Nucleic Acids Res 20: 1229-1233.
- Faber S, Wilcox K (1986) Association of the herpes simplex virus regulatory protein ICP4 with specific nucleotide sequences in DNA. Nucleic Acids Res 14: 6067-6083.
- Faber SW, Wilcox KW (1988) Association of herpes simplex virus regulatory protein ICP4 with sequences spanning the ICP4 gene transcription initiation site. Nucleic Acids Res 16: 555-570.
- Ginalski K, Elofsson A, Fischer D, Rychlewski L (2003) 3D-Jury: a simple approach to improve protein structure predictions. Bioinformatics 19: 1015-1018.
- Ginalski K, von Grotthuss M, Grishin NV, Rychlewski L (2004) Detecting distant homology with Meta-BASIC. Nucleic Acids Res 32: W576-W581.
- Grondin B, DeLuca N (2000) Herpes simplex virus type 1 ICP4 promotes transcription preinitiation complex formation by enhancing the binding of TFIID to DNA. J Virol 74: 11504-11510.
- Gu BH, Kuddus R, DeLuca NA (1995) Repression of activator-mediated transcription by herpes simplex virus ICP4 via a mechanism involving interactions with the basal transcription factors TATA-binding protein and TFIIB. Mol Cell Biol 15: 3618-3626.
- Harris MA, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R, Eilbeck K, Lewis S, Marshall B, Mungall C, Richter J, Rubin GM, Blake JA et al. (2004) The Gene Ontology (GO) database and informatics resource. Nucleic Acids Res 32: D258-D261.
- Jones DT (1999) Protein secondary structure prediction based on position-specific scoring matrices. J Mol Biol 292: 195-202.
- Knizewski L, Kinch L, Grishin NV, Rychlewski L, Ginalski K (2006) Human herpesvirus 1 UL24 gene encodes a potential PD-(D/E)XK endonuclease. J Virol 80: 2575-2577.
- Kolinski A (2004) Protein modeling and structure prediction with a reduced representation. Acta Biochim Polon 51: 349-371.
- Krwawicz J, Arczewska K, Speina E, Maciejewska A, Grzesiuk E (2007) Bacterial DNA repair genes and their eukaryotic homologues: 1. Mutations in genes involved in base excision repair (BER) and DNA-end processors and their implication in mutagenesis and human disease. Acta Biochim Polon 54: 413-434.
- Lang D, Powell SK, Plummer RS, Young KP, Ruggeri BA (2007) PAX genes: roles in development pathophysiology, cancer. Biochem Pharmacol 73: 1-14.
- Li W, Godzik A (2006) Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 22: 1658-1659.
- Linding R, Russell RB, Neduva V, Gibson TJ (2003) GlobPlot: Exploring protein sequences for globularity and disorder. Nucleic Acids Res 31: 3701-3708.
- McGeoch D, Dolan A, Donald S, Brauer DH (1986) Complete DNA sequence of the short repeat region in the genome of herpes simplex virus type 1. Nucleic Acids Res 14: 1727-1745.
- McGuffin LJ, Jones DT (2003) Improvement of the GenTHREADER method for genomic fold recognition. Bioinformatics 19: 874-881.
- Metzler D, Wilcox K (1985) Isolation of herpes simplex virus regulatory protein ICP4 as a homodimeric complex. J Virol 55: 329-337.
- Michael N, Roizman B (1989) Binding of the herpes simplex virus major regulatory protein to viral DNA. Proc Natl Acad Sci USA 86: 9808-9812.
- Pei J, Sadreyev R, Grishin NV (2003) PCMA: fast and accurate multiple sequence alignment based on profile consistency. Bioinformatics 19: 427-428.
- Rost B, Yachdav G, Liu J (2004) The PredictProtein server. Nucleic Acids Res 32: W321-W326.
- Smith C, Bates P, Rivera-Gonzalez R, Gu B, DeLuca NA (1993) ICP4 the major transcriptional regulatory protein of herpes simplex virus type 1 forms a tripartite complex with TATA-binding protein and TFIIB. J Virol 67: 4676-4687.
- Speina E, Ciesla JM, Graziewicz MA, Laval J, Kazimierczuk Z, Tudek B (2005) Inhibition of DNA repair glycosylases by base analogs and tryptophan pyrolysate Trp-P-1. Acta Biochim Polon 52: 167-178.
- Thompson J, Higgins D, Gibson T (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22: 4673-4680.
- Underhill DA (2000) Genetic and biochemical diversity in the Pax gene family. Biochem Cell Biol 78: 629-638.
- von Grotthuss M, Pas J, Wyrwicz L, Ginalski K, Rychlewski L (2003) Application of 3D-Jury GRDB, Verify3D in fold recognition. Proteins 53 (Suppl 6): 418-423.
- Wagner EK, Guzowski JF, Singh J (1995) Transcription of the herpes simplex virus genome during productive and latent infection. In Progress in Nucleic Acid Research and Molecular Biology (Cohn WH, Moldave K, ed) pp 123-165. San Diego CA: Academic Press.
- Watson RJ, Clements JB (1980) A herpes simplex virus type 1 function continuously required for early and late virus RNA synthesis. Nature 285: 329-30.
- Wintjens R, Rooman M (1996) Structural classification of HTH DNA-binding domains and protein-DNA interaction modes. J Mol Biol 262: 294-313.
- Wu C-L, Wilcox KW (1990) Codons 262 to 490 from the herpes simplex virus ICP4 gene are sufficient to encode a sequence-specific DNA binding protein. Nucleic Acids Res 18: 531-538.
- Wu C-L, Wilcox KW (1991) The conserved DNA-binding domains encoded by the herpes simplex virus type 1 ICP4 pseudorabies virus IE180, varicella-zoster virus ORF62 genes recognize similar sites in the corresponding promoters. J Virol 65: 1149-1159.
- Wyrwicz LS, Rychlewski L (2007a) Herpes glycoprotein gL is distantly related to chemokine receptor ligands. Antiviral Res 75: 83-86.
- Wyrwicz LS, Rychlewski L (2007b) Identification of Herpes TATT-binding protein. Antiviral Res 75: 167-172.
- Xia K, DeLuca N, Knipe D (1996) Analysis of phosphorylation sites of herpes simplex virus type 1 ICP4. J Virol 70: 1061-1071.
- Xu HE, Rould MA, Xu W, Epstein JA, Maas RL, Pabo CO (1999) Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding. Genes Dev 13: 1263-1275.
Publication order reference