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PDB:2C9L

Protein Name

ZEBRA protein complexed with double strand DNA

Species

Epstein-Barr virus (EBV, Human herpesvirus 4 (HHV-4))

Biological Context

More than 90% of the world population is infected with Epstein-Barr virus (EBV). EBV is a human herpesvirus that is tightly associated with several human malignancies. Once infected, a fraction of EBVs persist in the patient's B cells for a long time. Usually EBV is latent, but EBV sometimes reactivates on a periodic basis and replicates in a lytic manner in a subset of B cells, which enables EBV to be transmitted to next host. The lytic phase is triggered by the EBV immediate-early transcription factor ZEBRA (BZLF1, Zta, Z, EB1). ZEBRA binds to target sites termed ZEBRA response elements (ZREs) and activates the promoters of EBV lytic genes. Not only that, ZEBRA has many functions such as downregulating latency-associated promoters, replication factor, inducing host cell cycle arrest, altering cellular immune responses and ability of transcription factors. ZEBRA is a member of bZIP family of transcription factors, which include yeast GCN4 and human c-Fos and c-Jun. Through their bZIP domain, these protein dimerize and bind DNA. Among this family, ZEBRA is unique in that its bZIP domain lacks the heptad repeat of leucine residues that ordinarily mediates dimerization. In addition, ZEBRA's bZIP domain doesn't have ability to form a stable homodimer at physiological temperature or to bind DNA with high affinity. Lacking structural information, the way ZEBRA dimerizes and binds to DNA was not clear.

Structure Description

2c9l2c9l_x2c9l_y

The structure shown here is the ZEBRA-DNA complex. Two long bZIP helices forming a coiled coil, and like other bZIP proteins, ZEBRA homodimer grips the DNA like chopsticks. The C-terminal tails of bZIP helices forms additional motif, composed of a one-turn helix (helix alpha-C) followed by an extended stretch of residues runs antiparallel to the coiled coil. This C-terminal helix is connected to the bZIP by a hairpin turn. This structure stabilizes homodimer, alternative to missing leucine zipper motif. Compared to other bZIP proteins, ZEBRA more intimately contacts the phosphate backbone rather than bases, which may account for broader target site specificity than most bZIP proteins.

Protein Data Bank (PDB)

References

Source

  • Petosa, C. Morand, P. Baudin, F. Moulin, M. Artero, J.B. Muller, C.W.; "Structural basis of lytic cycle activation by the Epstein-Barr virus ZEBRA protein."; Mol.Cell; (2006) 21:565-572 PubMed:16483937.

Others

author: Miho Higurashi


Japanese version:PDB:2C9L