A short, disordered protein region mediates interactions between the homeodomain of the yeast alpha 2 protein and the MCM1 protein.
Homeodomains are folded into a characteristic three-dimensional structure capable of recognizing DNA in a sequence-specific manner. We show that correct target site selection by the yeast alpha 2 protein requires, as well as its homeodomain, an adjacent short and apparently unstructured region of the protein. This flexible homeodomain extension is responsible for specifying an interaction with a second regulatory protein, MCM1, which permits the cooperative binding of the two proteins to an operator. Two additional experiments suggest that this extension-homeodomain arrangement is likely to have some generality. First, when the extension of alpha 2 is grafted onto the Drosophila engrailed homeodomain, it yields a protein with the DNA binding specificity of engrailed and the ability to bind cooperatively to DNA with MCM1. Second, the alpha 2 extension specifies interaction not only with the yeast MCM1 protein, but also with the related human protein SRF.
Vershon
A K
AK
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Johnson
A D
AD
D000595:Amino Acid Sequence; D001483:Base Sequence; D004271:DNA, Fungal; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism*; D018398:Homeodomain Proteins; D006801:Humans; D026341:Minichromosome Maintenance 1 Protein; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D026362:Serum Response Factor; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D018398:Homeodomain Proteins; C062928:MATA2 protein, S cerevisiae; D026341:Minichromosome Maintenance 1 Protein; D009687:Nuclear Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D026362:Serum Response Factor; D014157:Transcription Factors