Analytical and Chromatography - Sigma

download report

Transcript Analytical and Chromatography - Sigma

Modular Structure of Transcription Factors
Modular Structure of Transcription Factors
• Transcription is an important step in gene expression that is regulated by the concerted action of
numerous transcription factors. These factors are proteins that recognize specific promoter
sequences and generally bind to them as homo- or heterodimers. Characteristically, transcription
factors have two functional components: a DNA-binding domain and a transactivation domain.
• DNA Binding Domains
Transcription factors are classified according to the structure of the DNA-binding domain including
basic helix-loop-helix, zinc finger, leucine zipper or high mobility group. The basic helix-loop-helix
structure contains two amphipathic -helices with highly conserved basic residues on the aminoterminal side and several hydrophobic residues on the carboxy-terminal end. The helices are linked
by amino acid sequences of variable length, which form reverse turns and loops and the entire motif
mediates homo- and heterodimerization, which favors DNA-binding through the basic domains. Zinc
finger transcription factors must recruit zinc in order to bind to DNA. There are two zinc finger motifs
that have been identified. The first consists of 30 amino acids, including two cysteine-histidine
pairings that coordinate tetrahedral binding to a single zinc atom. The second zinc finger motif
displays a partnership between cysteine-cysteine residues to direct zinc chelation. The leucine
zipper motif mediates DNA association in many different transcription factors including the protooncogene c-Myc, c-Fos and c-Jun. Like many other transcription factors, the leucine-zippercontaining transcription factors bind DNA as dimers. A leucine zipper is formed by two -helices, one
from each monomer. The helices are held together by hydrophobic interactions between leucine
residues, which are located on one side of each helix. The high mobility group box defines a class of
transcription factors. It binds to a 20bp span of DNA and distorts DNA structure. This motif is also a
feature of many structural and non-chromosomal proteins in the nucleus and can mediate bending,
wrapping, spacing and coiling of DNA.
Modular Structure of Transcription Factors
• Transactivation Domains
Following DNA binding, a transcription factor exerts an influence over gene expression. This is done through
interaction with other transcription factors or with the basal transcriptional machinery in order to affect the
efficiency of formation or binding of the transcription complex. These associations are often mediated through
a transactivation domain, which in most cases ranges from 30-100 amino acids in length and contain variable
functional amino acid arrangements such as glutamine- or proline-rich regions. Transactivation domains may
act directly or they may recruit coactivator proteins that possess activation properties and an ability to interact
with the basal transcription machinery, but these proteins lack any intrinsic DNA-binding capacity. For
example, cAMP responsive element binding protein (CREB) associates with CREB binding protein (CBP),
which in turn enhances gene transcription through activation of TFIIB. Alternatively, some transcription factors
mediate their effects by simply binding DNA and transmitting conformational changes through chromatin
structure. By doing this the transcription factor improves the accessibility of proteins to DNA binding sites.