Abstract
The cooperative binding of gene regulatory proteins to DNA is a common feature of transcriptional control in both prokaryotes and eukaryotes. It is generally viewed as a simple energy coupling, through protein-protein interactions, of two or more DNA-binding proteins. In this paper, we show that the simple view does not account for the cooperative DNA binding of a1 and alpha2, two homeodomain proteins from budding yeast. Rather, we show through the use of chimeric proteins and synthetic peptides that, upon heterodimerization, alpha2 instructs a1 to bind DNA. This change is induced by contact with a peptide contributed by alpha2, and this contact converts a1 from a weak to a strong DNA-binding protein. This explains, in part, how high DNA-binding specificity is achieved only when the two gene regulatory proteins conjoin. We also provide evidence that features of the a1-alpha2 interaction can serve as a model for other examples of protein-protein interactions, including that between the herpes virus transcriptional activator VP16 and the mammalian homeodomain-containing protein Oct-l.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Computer Graphics
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Dimerization
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Fungal Proteins / chemistry
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Fungal Proteins / metabolism
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Herpes Simplex Virus Protein Vmw65 / metabolism
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Homeodomain Proteins / chemistry
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Host Cell Factor C1
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Mammals
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Octamer Transcription Factor-1
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Oligodeoxyribonucleotides
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Protein Structure, Secondary
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / chemistry
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins
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Sequence Alignment
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Sequence Homology, Amino Acid
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Transcription Factors / metabolism
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Transcriptional Activation
Substances
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DNA-Binding Proteins
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Fungal Proteins
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Herpes Simplex Virus Protein Vmw65
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Homeodomain Proteins
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Host Cell Factor C1
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MATA2 protein, S cerevisiae
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Octamer Transcription Factor-1
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Oligodeoxyribonucleotides
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Recombinant Fusion Proteins
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors