Studies on protein-DNA interactions using the resonant recognition model. Application to repressors and transforming proteins.
The structural features of protein-DNA interactions have been evaluated using a new information theory algorithm for the analysis of protein structure/function dependence: the so-called resonant recognition model. The physicochemical basis of this analysis was firstly validated with the trp-repressor-operator interaction as a well-defined example. The amino acid and structural features predicted by these procedures to be crucial for repressor-operator interaction were found to be clustered around the known three-dimensional structure of the active site of the trp repressor. Similar methods of analysis have been extended to the less-well-defined example of the Ha-ras p21 protein family. The results of this analysis have indicated two distinct interactive regions in p21, one associated with the guanine-nucleotide-binding site, whilst the second is proposed to be associated with a binding site for an activator protein. These studies indicate that the p21 protein, besides the ability to function as a plasma-membrane-associated guanine-nucleotide-binding regulatory protein and bind free guanine nucleotides in the cytoplasm, has the structural ability to bind guanine incorporated in DNA. Thus, p21-related proteins may have the potential to function as an DNA-binding and regulating protein with the mode of upstream DNA binding closely related to their oncogenic function.
Cosic
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Department of Biochemistry, Monash University, Clayton, Australia.
Hearn
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D000818:Animals; D001426:Bacterial Proteins; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D015689:Oncogene Protein p21(ras) / Q000737:chemistry / Q000378:metabolism*; D015513:Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D029968:Escherichia coli Proteins
D001426:Bacterial Proteins; D004247:DNA; D015689:Oncogene Protein p21(ras); D015513:Oncogene Proteins; D012097:Repressor Proteins; C027190:TRPR protein, E coli; D029968:Escherichia coli Proteins