Insights into binding cooperativity of MATa1/MATα2 from the crystal structure of a MATa1 homeodomain‐maltose binding protein chimera

Abstract

The Yeast MAT a 1 and MATα2 are homeodomain proteins that bind DNA cooperatively to repress transcription of cell type specific genes. The DNA affinity and specificity of MAT a 1 in the absence of MATα2, however, is very low. MAT a 1 is converted to a higher affinity DNA‐binding protein by its interaction with the C‐terminal tail of MATα2. To understand why MAT a 1 binds DNA weakly by itself, and how the MATα2 tail affects the affinity of MAT a 1 for DNA, we determined the crystal structure of a maltose‐binding protein (MBP)‐ a 1 chimera whose DNA binding behavior is similar to MAT a 1. The overall MAT a 1 conformation in the MBP‐ a 1 structure, which was determined in the absence of α2 and DNA, is similar to that in the a 1/α2/DNA structure. The sole difference is in the C‐terminal portion of the DNA recognition helix of MAT a 1, which is flexible in the present structure. However, these residues are not in a location likely to be affected by binding of the MATα2 tail. The results argue against conformational changes in a1 induced by the tail of MATα2, suggesting instead that the MATα2 tail energetically couples the DNA binding of MATα2 and MAT a 1.