MOLECULAR INTERACTIONS OF A YEAST HOMEODOMAIN PROTEIN

Project Details

Description

Gene expression in eukaryotes is often under the control of multiple
nuclear proteins that work in combination to regulate transcription.
The combined interactions between these proteins will often create a
new form of regulatory activity that is distinctly different than the
function of either protein alone. The protein-protein interactions may
dictate whether a regulatory protein functions as a transcriptional
activator or repressor, as well as determine which genes are regulated
by the protein. We are interested in how the combined interactions
between these transcriptional regulatory proteins alter their function
and site of action. We have chosen to study this problem using a simple regulatory system
that determines cell type in the yeast Saccharomyces cerevisiae. This
system involves the alpha2 and a1 proteins, members of the highly
conserved homeodomain family of DNA-binding proteins; and MCM1, a
protein with strong sequence similarity to the DNA-binding domain of
the mammalian serum response factor, SRF. The alpha2 protein works in
combination with MCM1 to repress one set of genes, and with the a1 to
repress a different set of genes. Interactions between alpha2 and
MCM1, and alpha2 and a1 therefore determine the target specificity of
alpha2 repression. We are interested in how these protein-protein
interactions effect DNA-binding affinity and specificity of alpha2. We propose to: (1) Examine the mechanism of DNA binding by the alpha2
homeodomain. This analysis may indicate whether there are any general
principals that can be applied to DNA recognition by homeodomain
proteins in higher eukaryotes. (2) Determine how MCM1 binds DNA.
These experiments will provide knowledge about how members of this
growing class of DNA-binding proteins function. (3) Determine which
residues in alpha2 and MCM1 are involved in protein-protein
interactions between the two proteins, and how these interactions
effect the mechanism of DNA-binding by each protein. (4) Examine the
mechanism of DNA-binding by alpha2 when it is associated with the a1
protein. The proteins in this simple regulatory system are similar in
structure to regulatory proteins in mammals and plants. It therefore
seems likely that the information we learn about the interactions
between these classes of proteins will be relevant to more complex
systems in higher eukaryotes.
StatusFinished
Effective start/end date5/1/934/30/07

Funding

  • National Institutes of Health: $287,014.00
  • National Institutes of Health: $240,491.00
  • National Institutes of Health: $247,610.00
  • National Institutes of Health: $193,717.00
  • National Institutes of Health: $16,250.00
  • National Institutes of Health: $287,014.00
  • National Institutes of Health: $208,157.00
  • National Institutes of Health: $254,944.00
  • National Institutes of Health
  • National Institutes of Health: $188,314.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $287,014.00
  • National Institutes of Health: $287,014.00

ASJC

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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