DNA binding proteins have been extensively studied, but even today there exist no established rules for predicting DNA sequence specificity based upon the amino acid sequence of a protein. Homeodomain proteins provide a system with a highly conserved sequence of 60 amino acids spanning across most eukaryotic organisms that fulfill a basic regulatory function. This high degree of conservation makes them an ideal model system for studies attempting to elucidate specific protein-DNA interactions.
The role of these proteins in vivo is to control the genetic determination of developement and implementation of the genetic body plan. This, presumably, is why they are so highly conserved: they fulfill a function too vital to tolerate gross change in sequence or expression pattern. Interestingly, homeotic genes are organized on chromosomes in the same order as the body structure they control, from anterior to posterior.
The general structure of a homeodomain can be described as Helix-Loop-Helix-Turn-Helix, although in Antennapedia the third helix is generally considered to be composed of two helices. One might correctly identify these as Helix-Turn-Helix proteins, although the structure of a homeodomain is more stable and retains its function when isolated.
Specific interactions in Antennapedia, as determined by NMR, reveal most of the features common to homeodomain proteins. Other structures that one can obtain from Brookhaven protein databank are the Drosophila engrailed homeodomain and MAT alpha2 (which is an example of a homeodomain with divergent sequence.) The free program RasMol is very useful in viewing these kinds of complex structures.
Here is a summary of conserved specifc homedomain protein-DNA interactions.
Information in this project comes primarily from these references.
This page has been developed Donovan C. Haines as part of a VSNS-PPS course assignment. Email comments or problems to DCHaines@wsuhub.uc.twsu.edu.