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Science 13 October 1995:
Vol. 270. no. 5234, pp. 262 - 269
DOI: 10.1126/science.270.5234.262
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Research Articles

Crystal Structure of the MATa1/MAT2 Homeodomain Heterodimer Bound to DNA

Thomas Li,  Martha R. Stark,  Alexer D. Johnson,  Cynthia Wolberger (1)

The Saccharomyces cerevisiae MATa1 and MATalpha2 homeodomain proteins, which play a role in determining yeast cell type, form a heterodimer that binds DNA and represses transcription in a cell type-specific manner. Whereas the alpha2 and a1 proteins on their own have only modest affinity for DNA, the a1/alpha2 heterodimer binds DNA with high specificity and affinity. The three-dimensional crystal structure of the a1/alpha2 homeodomain heterodimer bound to DNA was determined at a resolution of 2.5 Å. The a1 and alpha2 homeo- domains bind in a head-to-tail orientation, with heterodimer contacts mediated by a 16-residue tail located carboxyl-terminal to the alpha2 homeodomain. This tail becomes ordered in the presence of a1, part of it forming a short amphipathic helix that packs against the a1 homeodomain between helices 1 and 2. A pronounced 60° bend is induced in the DNA, which makes possible protein-protein and protein-DNA contacts that could not take place in a straight DNA fragment. Complex formation mediated by flexible protein-recognition peptides attached to stably folded DNA binding domains may prove to be a general feature of the architecture of other classes of eukaryotic transcriptional regulators.

T. Li is in the Department of Biophysics and Biophysical Chemistry and C. Wolberger is in the Department of Biophysics and Biophysical Chemistry and the Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205-2185, USA. M. R. Stark and A. D. Johnson are in the Department of Microbiology and Immunology, University of California School of Medicine, San Francisco, CA 94143-0502, USA.  
(1) To whom correspondence should be addressed. 


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