Altered DNA Recognition and Bending by Insertions in the 
2
Tail of the Yeast a1/
2 Homeodomain Heterodimer
Yisheng Jin,
Janet Mead,
Thomas Li,
Cynthia Wolberger,
Andrew K. Vershon (1)
The yeast MAT
2 and MATa1 homeodomain proteins bind
cooperatively as a heterodimer to sites upstream of haploid-specific
genes, repressing their transcription. In the crystal structure of 2
and a1 bound to DNA, each homeodomain makes independent
base-specific contacts with the DNA and the two proteins contact each
other through an extended tail region of 2 that tethers the two
homeodomains to one another. Because this extended region may be
flexible, the ability of the heterodimer to discriminate among DNA
sites with altered spacing between 2 and a1 binding sites
was examined. Spacing between the half sites was critical for specific
DNA binding and transcriptional repression by the complex. However,
amino acid insertions in the tail region of 2 suppressed the effect
of altering an a1/2 site by increasing the spacing
between the half sites. Insertions in the tail also decreased DNA
bending by a1/2. Thus tethering the two homeodomains
contributes to DNA bending by a1/2, but the precise
nature of the resulting bend is not essential for repression.
Y. Jin, J. Mead, A. K. Vershon, Waksman Institute and Department
of Molecular Biology and Biochemistry, Rutgers University, Piscataway,
NJ 08855-0759, USA. T. Li, Department of Biophysics and Biophysical Chemistry, Johns
Hopkins University School of Medicine, Baltimore, MD 21205-2185, USA. C. Wolberger, Howard Hughes Medical Institute and Department of
Biophysics and Biophysical Chemistry, Johns Hopkins University School
of Medicine, Baltimore, MD 21205-2185, USA.
(1) To whom correspondence should be addressed.
