Transcription factor c-Fos-c-Jun / DNA complex
Homo sapiens (Human)
Proto-oncogenes are normal-cell genes that, when mutated or abnormally expressed, induce cell proliferation and tumor development. Fos and Jun are the protein products of such proto-oncogenes. Fos and Jun bind to one another, or heterodimerize, to form the activator protein 1 (AP1) transcription factor. Transcription factors regulate the expression of genes in DNA by binding to it and helping the RNA polymerase (protein that transcribes RNA from DNA) bind to the promoter region, where RNA synthesis starts. This increases the transcription of DNA to RNA from that region resulting in the up-regulation of gene expression. AP1 binds to 5'-TGAGTCA-3' regions of DNA and positively regulates target genes leading to cell division.
The structure here is that of a heterodimer of the basic-region-leucine zipper (bZIP) regions of c-Fos and c-Jun bound to DNA like a pair of forceps. As seen here, c-Fos and c-Jun form continuous alpha-helices interacting in the bZIP domain, resulting in an asymmetric coiled-coil in the carboxy-terminal regions. The subunits then split to make contacts with specific bases in the major groove of DNA. The c-Jun subunit is slightly curled as compared to the c-Fos subunit. Identification of two distinct crystal structures representing 180 degrees rotations about the axis of the dimer suggests that the Fos-Jun heterodimer has no preference for the orientation in which it binds the AP1 site on DNA (i.e. it can bind 5'-TGAGTCA-3' or 5'-TGACTCA-3') and that the coiled coil is flexibly joined to the basic regions. The formation of the Jun-Fos heterodimer is favoured over that of the Jun-Jun or Fos-Fos homodimers due to a large network of electrostatic interactions between the Jun and Fos subunits.
Protein Data Bank (PDB)
Glover, J.N. Harrison, S.C.; "Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA."; Nature; (1995) 373:257-261 PubMed:7816143.
author: Ashwini Patil