MAT Homeodomain-DNA Structure
Li, 1995. Crystal structure of the MATa1/MATalpha2 homeodomain
heterodimer bound to DNA Science 270, 262-269. [Medline
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The A1/alpha2 - DNA Complex exhibits several properties which
are important in DNA protein interactions:
- Combinatorial binding of proteins to DNA
- Protein-protein interactions
- DNA bending induced by protein binding
- H-bonding and water mediated H-bonding
a1 and alpha2
regulate yeast mating type loci:
- diploid cells: a1/alpha2
formed - shuts off haploid-specific genes
- haploid (alpha) cells: MCM1/alpha2
formed - shuts off a-specific genes
So MCM1 and a1 can change
binding specificity of alpha2.
All are homeodomain proteins- originally discovered in Drosophila
homeotic genes, a gene family with a conserved 60 aa sequence
near the C-terminus (the homeodomain). Many have been shown
to regulate development in various organisms. They belong to the
"helix-turn-helix" class of DNA binding proteins and
often act in combination with other homodomain proteins. The "helix-turn-helix"
proteins have an alpha helix which fits into the major groove
of the DNA, backed by 2 alpha helices which lay across the groove.
Both a1 and alpha2
bind DNA by themselves, but with low affinity and specificity.
Both binding specificity and affinity are increased 105-fold
when they bind as a homeodimer. Binding is dependent on presence
of both binding sites at proper spacing.
The sequences above are sites to which the a1/alpha2 heterodimer binds in vivo.
The boxed regions are conserved in at least 75% of the yeast binding
sites for MATa1/alpha2. Note that the conserved regions are spaced
the same distance apart at all sites.
II. The complex
The crystal structure of the a1/alpha2 heterodimer complexed with
DNA is shown at left, similar to Fig1a of the reference. To make
the coloring match the refernce and the rest of the figures of
this tutorial, click this button
III. Protein-protein interaction
protein-protein interaction can be seen by clicking here
IV. Protein-DNA contacts
A diagram of the DNA-protein contacts is shown below. H-bonds
are indicated by arrows, and the proteins are color coded as above.
Water molecules involved in H-bonds are shown as blue "w"
s. Conserved nucleotides are shown in green.
to intro to DNA-RNA structure.
This section Still Under Construction
Comments or Suggestions to:Jim
Nolan at James.M.Nolan@tulane.edu