Protein Engineering vol. 4 no. 8 pp. 891-901, 1991
© 1991 Oxford University Press
RESEARCH-ARTICLE |
Proposed structure for the DNA-binding domain of the Myb oncoprotein based on model building and mutational analysis
European Molecular Biology Laboratory Postfach 10,2209. Meyerhofstrasse 1, Heidelberg, Germany
1To whom correspondence should be addressed
Myb-related proteins from plants to humans are characterized by a DNA-binding domain which contains two to three imperfect repeats of {small tilde}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.
Keywords: helix-turn-helix motif/molecular modelling/Myb DNA-binding domain/oligonucleotide-directed mutagenesis
Received June 25, 1991; accepted September 30, 1991.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Jia, M. T. Clegg, and T. Jiang Evolutionary Dynamics of the DNA-Binding Domains in Putative R2R3-MYB Genes Identified from Rice Subspecies indica and japonica Genomes Plant Physiology, February 1, 2004; 134(2): 575 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Andersson, E. Kowenz-Leutz, E. M. Brendeford, A.-H. H. Tygsett, A. Leutz, and O. S. Gabrielsen Phosphorylation-dependent Down-regulation of c-Myb DNA Binding Is Abrogated by a Point Mutation in the v-myb Oncogene J. Biol. Chem., January 31, 2003; 278(6): 3816 - 3824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Luchetti, P. Paroncini, P. Majlingova, J. Frampton, M. Mucenski, S. S. Baroni, P. Sambo, J. Golay, M. Introna, and A. Gabrielli Characterization of the c-Myb-responsive Region and Regulation of the Human Type I Collagen alpha 2 Chain Gene by c-Myb J. Biol. Chem., January 10, 2003; 278(3): 1533 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-A. Lu, T.-h. D. Ho, S.-L. Ho, and S.-M. Yu Three Novel MYB Proteins with One DNA Binding Repeat Mediate Sugar and Hormone Regulation of {alpha}-Amylase Gene Expression PLANT CELL, August 1, 2002; 14(8): 1963 - 1980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bergholtz, T. O. Andersen, K. B. Andersson, J. Borrebak, B. Luscher, and O. S. Gabrielsen The highly conserved DNA-binding domains of A-, B- and c-Myb differ with respect to DNA-binding, phosphorylation and redox properties Nucleic Acids Res., September 1, 2001; 29(17): 3546 - 3556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Nesi, C. Jond, I. Debeaujon, M. Caboche, and L. Lepiniec The Arabidopsis TT2 Gene Encodes an R2R3 MYB Domain Protein That Acts as a Key Determinant for Proanthocyanidin Accumulation in Developing Seed PLANT CELL, September 1, 2001; 13(9): 2099 - 2114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pinson, E. M. Brendeford, O. S. Gabrielsen, and B. Daignan-Fornier Highly conserved features of DNA binding between two divergent members of the Myb family of transcription factors Nucleic Acids Res., January 15, 2001; 29(2): 527 - 535. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.-J. Park, D. J. Schroen, M. Yang, H. Li, L. Li, and J. D. Chen SMRTe, a silencing mediator for retinoid and thyroid hormone receptors-extended isoform that is more related to the nuclear receptor corepressor PNAS, March 30, 1999; 96(7): 3519 - 3524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Guo, C Anjard, A Harwood, H. Kim, P. Newell, and J. Gross A myb-related protein required for culmination in Dictyostelium Development, January 6, 1999; 126(12): 2813 - 2822. [Abstract] [PDF]
|
|
|
|
 |
|
 J. Kehle, D. Beuchle, S. Treuheit, B. Christen, J. A. Kennison, M. Bienz, and J. Müller dMi-2, a Hunchback-Interacting Protein That Functions in Polycomb Repression Science, December 4, 1998; 282(5395): 1897 - 1900. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Ohi, A. Feoktistova, S. McCann, V. Valentine, A. T. Look, J. S. Lipsick, and K. L. Gould Myb-Related Schizosaccharomyces pombe cdc5p Is Structurally and Functionally Conserved in Eukaryotes Mol. Cell. Biol., July 1, 1998; 18(7): 4097 - 4108. [Abstract] [Full Text]
|
|
|
|
|
|
M. Oda, K. Furukawa, K. Ogata, A. Sarai, S. Ishii, Y. Nishimura, and H. Nakamura Investigation of the Pyrimidine Preference by the c-Myb DNA-binding Domain at the Initial Base of the Consensus Sequence J. Biol. Chem., July 18, 1997; 272(29): 17966 - 17971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Brendeford, A. H. Myrset, A. B. Hegvold, M. Lundin, and O. S. Gabrielsen Oncogenic Point Mutations Induce Altered Conformation, Redox Sensitivity, and DNA Binding in the Minimal DNA Binding Domain of Avian Myeloblastosis Virus v-Myb J. Biol. Chem., February 14, 1997; 272(7): 4436 - 4443. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Solano, A. Fuertes, L. Sanchez-Pulido, A. Valencia, and J. Paz-Ares A Single Residue Substitution Causes a Switch from the Dual DNA Binding Specificity of Plant Transcription Factor MYB.Ph3 to the Animal c-MYB Specificity J. Biol. Chem., January 31, 1997; 272(5): 2889 - 2895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Williams and E. Grotewold Differences between Plant and Animal Myb Domains Are Fundamental for DNA Binding Activity, and Chimeric Myb Domains Have Novel DNA Binding Specificities J. Biol. Chem., January 3, 1997; 272(1): 563 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Miglarese, A. F. Richardson, N. Aziz, and T. P. Bender Differential Regulation of c-Myb-induced Transcription Activation by a Phosphorylation Site in the Negative Regulatory Domain J. Biol. Chem., September 13, 1996; 271(37): 22697 - 22705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Clark and D. McKearin The Drosophila stonewall gene encodes a putative transcription factor essential for germ cell development Development, January 3, 1996; 122(3): 937 - 950. [Abstract] [PDF]
|
|
|
|
 |
|
 J Wieser and T H Adams flbD encodes a Myb-like DNA-binding protein that coordinates initiation of Aspergillus nidulans conidiophore development. Genes & Dev., February 15, 1995; 9(4): 491 - 502. [Abstract] [PDF]
|
|
|
|
|
|
Y O Yuan, I L Stroke, and S Fields Coupling of cell identity to signal response in yeast: interaction between the alpha 1 and STE12 proteins. Genes & Dev., August 1, 1993; 7(8): 1584 - 1597. [Abstract] [PDF]
|
|
|
|
|
|
S A Ness, E Kowenz-Leutz, T Casini, T Graf, and A Leutz Myb and NF-M: combinatorial activators of myeloid genes in heterologous cell types. Genes & Dev., May 1, 1993; 7(5): 749 - 759. [Abstract] [PDF]
|
|