2NNU

Crystal Structure of the Papillomavirus DNA Tethering Complex E2:Brd4

Summary for 2NNU

• Entry DOI: 10.2210/pdb2nnu/pdb
• Descriptor: Regulatory protein E2, Bromodomain-containing protein 4 (3 entities in total)
• Functional Keywords: protein-peptide complex, helical peptide, three helix bundle, amphipathic helix, transcription
• Biological source: Human papillomavirus type 16; More
• Cellular location: Host nucleus: P03120; Nucleus (By similarity): O60885
• Total number of polymer chains: 2
• Total formula weight: 26307.57

Authors

Abbate, E.A.,Voitenleitner, C.,Botchan, M.R. (deposition date: 2006-10-24, release date: 2007-01-09, Last modification date: 2023-08-30)

Primary citation

Abbate, E.A.,Voitenleitner, C.,Botchan, M.R.
Structure of the Papillomavirus DNA-Tethering Complex E2:Brd4 and a Peptide that Ablates HPV Chromosomal Association.
Mol.Cell, 24:877-889, 2006

PubMed Abstract: Many 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.

PubMed: 17189190
DOI: 10.1016/j.molcel.2006.11.002

Experimental method

X-RAY DIFFRACTION (1.59 Å)