Protein Domain : Papillomavirus E2, C-terminal IPR000427

Type	Domain
Description	E2 is an early regulatory protein found in the dsDNA papillomaviruses. The viral genome is a 7.9-kb circular DNA that codes for at least eight early and two late (capsid) proteins. The products of the early genes E6 and E7 are oncoproteins that destabilise the cellular tumour suppressors p53 and pRB. The product of the E1 gene is a helicase necessary for viral DNA replication. The products of the E2 gene play key roles in the regulation of viral gene transcription and DNA replication. During early stages of viral infection, the E2 protein represses the transcription of the oncogenes E6 and E7, reintroduction of E2 into cervical cancer cell-lines leads to repression of E6/E7 transcription, stabilisation of the tumour suppressor p53, andcell-cycle arrest at the G1 phase of the cell cycle. E2 can also induce apoptosis by a p53-independent mechanism. E2 proteins from all papillomavirus strains bind a consensus palindromic sequence ACCgNNNNcGGT present in multiple copies in the regulatory region. It can either activate or repress transcription, depending on E2RE's position with regard to proximal promoter elements. Repression occurs by sterically hindering the assembly of the transcription initiation complex. The E2 protein is composed of a C-terminal DNA-binding domain and an N-terminal trans-activation domain. E2 exists in solution and binds to DNA as a dimer The E2-DNA binding domain forms a dimeric β-barrel, with each subunit contributing an anti-parallel 4-stranded β-sheet "half-barrel"[ , ]. The topology of each subunit is beta1-1-beta2-beta3-2-beta4. Helix 1 is the recognition helix housing all of the amino acid residues involved in direct DNA sequence specification. Upon dimerisation, strands beta2 and beta4 at the edges of each subunit participate in a continuous hydrogen-bonding network, which results in an 8-stranded β-barrel. The dimer interface is extensive, made up of hydrogen bondsbetween subunits and a substantial hydrophobic β-barrel core.
Short Name	Papillomavirus_E2_C