2nnu
From Proteopedia
Crystal Structure of the Papillomavirus DNA Tethering Complex E2:Brd4
Structural highlights
FunctionVE2_HPV16 Plays an accessory role in initiation of DNA replication. A dimer of E2 interacts with a dimer of E1 in order to improve specificity of E1 DNA binding activity. Once the complex recognizes and binds DNA at specific sites, the E2 dimer is removed from DNA. E2 also regulates viral transcription through binding to the E2RE response element (5'-ACCNNNNNNGGT-3') present in multiple copies in the regulatory regions of the viral genome. Activates or represses transcription depending on E2RE's position with regards to proximal promoter elements including the TATA-box. Repression occurs by sterically hindering the assembly of the transcription initiation complex.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMany DNA viruses that are latent in dividing cells are noncovalent passengers on mitotic chromosomes and require specific viral-encoded and cellular factors for this activity. The chromosomal protein Brd4 is implicated in the hitchhiking of bovine papillomavirus-1 (BPV-1), and the viral protein E2 binds to both plasmids and Brd4. Here, we present the X-ray crystal structure of the carboxy-terminal domain of Brd4 in complex with HPV-16 E2, and with this information have developed a Brd4-Tat fusion protein that is efficiently taken up by different transformed cells harboring HPV plasmids. In cells treated with these fusion proteins for only 2 hr and arrested in metaphase, the HPV DNA, either HPV-16 or -31, is displaced from mitotic chromosomes. Mutant Brd4 peptides are deficient in ablating this association. We suggest that such peptides may lead to the development of inhibitors of latency for many, if not all, papillomaviruses. Structure of the papillomavirus DNA-tethering complex E2:Brd4 and a peptide that ablates HPV chromosomal association.,Abbate EA, Voitenleitner C, Botchan MR Mol Cell. 2006 Dec 28;24(6):877-89. PMID:17189190[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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