Identification of Herpes TATT-binding protein

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.