Proposed structure for the DNA-binding domain of the Myb oncoprotein based on model building and mutational analysis

Myb-related proteins from plants to humans are characterized by a DNA-binding domain which contains two to three imperfect repeats of ˜50 amino acids each. Based on the evolutionary conservation of specific residues, secondary structural predictions suggest an arrangement of a helices homologous to...

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Bibliographic Details
Published in:Protein engineering 1991-12, Vol.4 (8), p.891-901
Main Authors: Frampton, J., Gibson, T.J., Ness, S.A., Döderlein, G., Graf, T.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Analytical, structural and metabolic biochemistry
Binding and carrier proteins
Binding Sites
Biological and medical sciences
DNA Mutational Analysis
DNA-Binding Proteins - chemistry
DNA-Binding Proteins - genetics
Fundamental and applied biological sciences. Psychology
helix-turn-helix motif
Models, Molecular
molecular modelling
Molecular Sequence Data
Multigene Family
Mutagenesis, Site-Directed
Myb DNA-binding domain
oligonucleotide-directed mutagenesis
Protein Conformation
Proteins
Proto-Oncogene Proteins - chemistry
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-myb
Regulatory Sequences, Nucleic Acid
Sequence Homology, Nucleic Acid
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Summary:Myb-related proteins from plants to humans are characterized by a DNA-binding domain which contains two to three imperfect repeats of ˜50 amino acids each. Based on the evolutionary conservation of specific residues, secondary structural predictions suggest an arrangement of a helices homologous to that seen in the homeodomains, members of the helix-turn-helix family of DNA-binding proteins. We have used molecular modelling in conjunction with site-directed mutagenesis to test the feasibility of this structure. We propose that each Myb repeat consists of three a helices packed over a hydrophobic core which is built around the three highly conserved tryptophan residues. The C-terminal helix forms part of the helix-turn-helix motif and can be positioned into the major groove of B-form DNA, allowing prediction of residues critical for specificity of interaction. Modelling also allowed positioning of adjacent repeats around the major groove over an 8 bp binding site.
ISSN:1741-0126
0269-2139
1741-0134
1460-213X
DOI:10.1093/protein/4.8.891