Domains of the Epstein-Barr virus (EBV) transcription factor R required for dimerization, DNA binding and activation.
In cells latently infected with EBV, the switch from latency to a productive infection is linked to the expression of two transcriptional activators, the upstream element factor EB1 and the enhancer factor R. R activates by interacting directly with specific DNA sequences called RREs (R Responsive Elements). Each binding site covers about 18 bp, where R simultaneously contacts two core sequences separated by 5 to 7 bp (1). Here we show that R binds in vitro as a homodimer to an RRE, and that stable homodimers can also form in solution in the absence of DNA. By functional analysis of deletion and insertion mutants of R, we have localized the DNA binding region within the 280 N-terminal amino acids and the dimerization region within the 232 N-terminal amino acids. As no obvious homologies were detected with other known DNA binding or dimerization motifs, R could contain novel protein structures mediating these functions. The transcriptional activation domain has been located in the C-terminal half of the protein. This domain contains two regions with structures already identified in other transcription factors: one region is rich in proline, the other rich in acidic residues.
Manet
E
E
Laboratoire de Virologie Moléculaire, Ecole Normale Supérieure de Lyon, UMR 49 CNRS-ENS, France.
Rigolet
A
A
Gruffat
H
H
Giot
J F
JF
Sergeant
A
A
D001483:Base Sequence; D001665:Binding Sites; D004279:DNA, Viral / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics*; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011233:Precipitin Tests; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014764:Viral Proteins; D014775:Virus Activation
C068382:BRLF1 protein, Human herpesvirus 4; D004279:DNA, Viral; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014764:Viral Proteins