In this part of this practical we will look in structural
at a number of
examples of the specific recognition between DNA and proteins and
it is controlled.
A prokaryotic repressor
An example of a prokaryotic
repressor is the trp repressor, which regulates the synthesis of the
amino acid tryptophan by negative feed-back. A schematic view of
control is shown in this figure.
The protein is a dimer
binding to an inverted repeat in the DNA. The protein has a
helix-turn-helix motif which is found in many bacterial repressors.
A PDB entry of a protein-DNA
complex is found, as well as entries for various other forms of the
Download the complex. The DNA in the complex is a variant of the
DNA operon to which the protein normally binds. Locate the
helix-turn-helix motif in the repressor!
Q. 1. What are the nature of
direct contacts between the protein and the DNA? Are
there any hydrogen
Download also the repressor without the tryptophan (the
Superimpose the proteins and compare the conformation of the
with and without the amino
Q. 2. What changes occur in the
Q. 3. How can that explain the
of the tryptophan?
Eukaryotic transcription factors
Eukaryotic transcription factors have widely different types of
There are some families of transcription factors with
motifs. Other types of transcription factors still bind to DNA using
alpha helix in the major groove. We will look at a couple of
to see some of the variability in their folds.
Zinc finger domains
A number of transcription factors are called zinc fingers, but they
divided in a number of families that are
not really related. One type is what is also called the classic Zn
finger domain. An example is the Zif268 protein, a mammalian protein
now called Egr1 (Early growth response 1). The protein has 543 amino
acids. There are three Zn-finger domains in the protein and in the
database SMART it is drawn like this (the purple rectangles
"low-complexity regions", possibly flexible regions in the protein.
The crystal structure is known only for the DNA-binding part of the
protein. Download this protein
in complex with DNA!
Q. 4. How are the Zn ions
coordinated? What is the role of the Zn ion in the
Q. 5. Describe how the
binds to the DNA! What hydrogen bonds between the
protein and the DNA
do you find (use only one of the Zn fingers)?
Another type of Zn finger is found in the DNA-binding domain of
the glucocorticoid receptor.
Q. 6. How are the Zn ions
coordinated in this protein?
Q. 7. How is the DNA
in this complex?
Many transcription factors have a simple design using a leucine
to form a dimer. The leucine zipper is a short coiled-coil of alpha
Find a leucine zipper-DNA complex in the data bank.
Q. 8. How is the DNA bound
The zipper region is characterized by a regular pattern of leucine
with a distance of 7 amino acid residues along the sequence.
Q. 9. Explain this pattern
looking at the interactions in the zipper region!
"Transcription", Lars Liljas