Homeodomains are folded into a characteristic three-dimensional structure capable of recognizing DNA in a sequence-specific manner. We show that correct target site selection by the yeast α2 protein requires, as well as its homeodomain, an adjacent short and apparently unstructured region of the protein. This flexible homeodomain extension is responsible for specifying an interaction with a second regulatory protein, MCM1, which permits the cooperative binding of the two proteins to an operator. Two additional experiments suggest that this extension-homeodomain arrangement is likely to have some generality. First, when the extension of α2 is grafted onto the Drosophila engrailed homeodomain, it yields a protein with the DNA binding specificity of engrailed and the ability to bind cooperatively to DNA with MCM1. Second, the α2 extension specifies interaction not only with the yeast MCM1 protein, but also with the related human protein SRF.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)