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Insights into binding cooperativity of MATa1/MAT2 from the crystal structure of a MATa1 homeodomain-maltose binding protein chimera

¹ Department of Biophysics and Biophysical Chemistry
² Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

Reprint requests to: Cynthia Wolberger, Department of Biophysics and Biophysical Chemistry, Johns Hopkins University, School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA; e-mail: cwolberg{at}jhmi.edu; fax: 410-614-8648.

The Yeast MATa1 and MAT2 are homeodomain proteins that bind DNA cooperatively to repress transcription of cell type specific genes. The DNA affinity and specificity of MATa1 in the absence of MAT2, however, is very low. MATa1 is converted to a higher affinity DNA-binding protein by its interaction with the C-terminal tail of MAT2. To understand why MATa1 binds DNA weakly by itself, and how the MAT2 tail affects the affinity of MATa1 for DNA, we determined the crystal structure of a maltose-binding protein (MBP)-a1 chimera whose DNA binding behavior is similar to MATa1. The overall MATa1 conformation in the MBP-a1 structure, which was determined in the absence of 2 and DNA, is similar to that in the a1/2/DNA structure. The sole difference is in the C-terminal portion of the DNA recognition helix of MATa1, which is flexible in the present structure. However, these residues are not in a location likely to be affected by binding of the MAT2 tail. The results argue against conformational changes in a1 induced by the tail of MAT2, suggesting instead that the MAT2 tail energetically couples the DNA binding of MAT2 and MATa1.

Keywords: Homeodomain; MATa1; transcription; crystal structure; protein–DNA interactions; maltose binding protein; protein chimera

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