On this page, you can see a portion of the Gal4 homodimer bound to a
double-stranded DNA molecule. Gal4 is a transcription factor that is
involved in galactose metabolism (1). To function, Gal4 binds DNA in a
sequence specific manner and activates transcription (1). While it
spins,
notice the two
macromolecules: the protein (blue) and the DNA (red).
Reset
this protein-DNA complex.
Notice
the similarity between the two amino acid chains (blue and
green). The Gal4 transcription factor binds DNA as a homodimer
(two identical subunits form a complex that binds the DNA
molecule). This feature of Gal4 is essential to function
(1).
Look
closely at the DNA-binding
domain (residues 7-40, Orange).
Gal4 interacts with the DNA with this short DNA-binding motif.
Notice the way the ends of the Gal4 molecule fit into the major grooves
of the DNA.
Look
closely at the interaction with DNA. Notice the zinc ions (green)
that are present! Gal4 has a DNA-binding motif that is known as a
zinc-finger motif, due to the
presence of zinc ions in the complex
(1). Zinc fingers are one of many DNA binding motifs that have
been identified (2).
How
many base pairs does this protein recognize? Although this
Gal4 molecule is bound to a 20 base pair sequence of DNA, studies have
shown that it recognizes a specific 17 base pair sequence (3 of the
base pairs shown here are therefore not nocessary for recognition)
(1).
Also
notice the molecule (white) that is situated between the protein and
DNA. This molecule is known as MPD, or methyl-pentadiol. It
is a commonly used reagent in crystallizing proteins, but not part of
the structure in vivo.
Now
look at the rest of the protein (blue).
Notice
how the two subunits interact with one another. The dimerization
domain (residues 50-94, yellow) of each chain intertwine another
holding the
dimer together (1). This has been shown to be important in proper
DNA
binding of Gal4. When it is a monomore it binds with a
significantly lower affinity (see Gal4
Information) (1).
What
other domain is necessary for a functioning transcription factor?
The activation domain is not
actually shown here. This domain is
imoportant in the actual initiation of transcription, but was not part
of the structure used for this Jmol tutorial. The activation
domain would be attached to the ends of this portion of Gal4 (yellow).
References
1. Hong M, Fitzgerald M, Harper S, Lueo C, Speicher
D, Marmorstein R. Structural basis for dimerization in DNA recognition
by Gal4. Structure 2008; 16: 1019-1026.
2. Marmorstein R, Carey M, Ptashne M, Harrison S. DNA
recognition by GAL4: structure of a protein-DNA complex. Nature 1992;
256; 408-414.
