Abstract
TWO yeast homeodomain proteins, al and α2, interact and cooperatively bind the haploid-specific gene (hsg) operator, resulting in the repression of a set of genes involved in the determination of cell type1–5. The cooperative binding of al and α2 to DNA can be reconstituted in vitro using purified fragments of al and α2. Only the homeodomain is needed for al, but for α2 a C-terminal 22-amino-acid tail is required as well4,6–9. As most of the specificity of DNA binding appears to derive from al, we proposed4 that α2 functions in the al/α2 heterodimer to contact al with its tail. By construction and analysis of several chimaeric proteins, we investigate how two DNA-binding proteins, one with low intrinsic specificity (α2) and one with no apparent intrinsic DNA-binding ability (al), can together create a highly specific DNA-binding activity4. We show that the 22-amino-acid region of α2 immediately C-terminal to the homeodomain, when grafted onto the al homeodomain, converts al to a strong DNA-binding protein. This α2 tail can also be attached to the Drosophila engrailed homeodomain, and the chimaeric protein now binds cooperatively to DNA with al, showing how a simple change can create a new homeodomain combination that specifically recognizes a new DNA operator.
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Stark, M., Johnson, A. Interaction between two homeodomain proteins is specified by a short C-terminal tail. Nature 371, 429–432 (1994). https://doi.org/10.1038/371429a0
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DOI: https://doi.org/10.1038/371429a0
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