Role of tryptophan repeats and flanking amino acids in Myb-DNA interactions - PubMed (original) (raw)
Comparative Study
Role of tryptophan repeats and flanking amino acids in Myb-DNA interactions
P Saikumar et al. Proc Natl Acad Sci U S A. 1990 Nov.
Abstract
The c-myb protooncogene codes for a sequence-specific DNA-binding protein that appears to act as a transcriptional regulator and is highly conserved through evolution. The DNA-binding domain of Myb has been shown to contain three imperfectly conserved repeats of 52 amino acids that constitute the amino-terminal end. Within each repeat, there are three tryptophans that are separated by 18 or 19 amino acids and are flanked by basic amino acids. To determine the role of tryptophans and the flanking basic amino acids in the DNA-binding activity of Myb proteins, we have selectively mutagenized individual tryptophans as well as some of the amino acid residues that flank these tryptophans. Replacement of these tryptophans with glycine, proline, or arginine abolished the DNA-binding activity whereas replacement with other aromatic amino acids or leucine or alanine did not appreciably affect this activity. On the other hand the replacement of two amino acids, asparagine and lysine, that flank the last tryptophan with acidic amino acids completely abolished their DNA-binding activity. These results are consistent with a model we present in which the tryptophans form a hydrophobic scaffold that plays a crucial role in maintaining the helix-turn-helix structure of the DNA binding domain. Basic and polar amino acids adjacent to these tryptophans seem to participate directly in DNA binding.
Similar articles
- The tryptophan cluster: a hypothetical structure of the DNA-binding domain of the myb protooncogene product.
Kanei-Ishii C, Sarai A, Sawazaki T, Nakagoshi H, He DN, Ogata K, Nishimura Y, Ishii S. Kanei-Ishii C, et al. J Biol Chem. 1990 Nov 15;265(32):19990-5. J Biol Chem. 1990. PMID: 2246275 - Specific DNA binding by c-Myb: evidence for a double helix-turn-helix-related motif.
Gabrielsen OS, Sentenac A, Fromageot P. Gabrielsen OS, et al. Science. 1991 Sep 6;253(5024):1140-3. doi: 10.1126/science.1887237. Science. 1991. PMID: 1887237 - Solution structure of a DNA-binding unit of Myb: a helix-turn-helix-related motif with conserved tryptophans forming a hydrophobic core.
Ogata K, Hojo H, Aimoto S, Nakai T, Nakamura H, Sarai A, Ishii S, Nishimura Y. Ogata K, et al. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6428-32. doi: 10.1073/pnas.89.14.6428. Proc Natl Acad Sci U S A. 1992. PMID: 1631139 Free PMC article. - The myb and myc nuclear oncogenes as transcriptional activators.
Cole MD. Cole MD. Curr Opin Cell Biol. 1990 Jun;2(3):502-8. doi: 10.1016/0955-0674(90)90134-z. Curr Opin Cell Biol. 1990. PMID: 2198899 Review. No abstract available. - Molecular astrology: the case of the Myb DNA binding domain.
Murthy K. Murthy K. Protein Eng. 1993 Feb;6(2):129-31. doi: 10.1093/protein/6.2.129. Protein Eng. 1993. PMID: 8475040 Review. No abstract available.
Cited by
- Coordinate regulation of replication and virion sense gene expression in wheat dwarf virus.
Hofer JM, Dekker EL, Reynolds HV, Woolston CJ, Cox BS, Mullineaux PM. Hofer JM, et al. Plant Cell. 1992 Feb;4(2):213-23. doi: 10.1105/tpc.4.2.213. Plant Cell. 1992. PMID: 1633494 Free PMC article. - Highly conserved features of DNA binding between two divergent members of the Myb family of transcription factors.
Pinson B, Brendeford EM, Gabrielsen OS, Daignan-Fornier B. Pinson B, et al. Nucleic Acids Res. 2001 Jan 15;29(2):527-35. doi: 10.1093/nar/29.2.527. Nucleic Acids Res. 2001. PMID: 11139623 Free PMC article. - Molecular recognition in complexes of TRF proteins with telomeric DNA.
Wieczór M, Tobiszewski A, Wityk P, Tomiczek B, Czub J. Wieczór M, et al. PLoS One. 2014 Feb 26;9(2):e89460. doi: 10.1371/journal.pone.0089460. eCollection 2014. PLoS One. 2014. PMID: 24586793 Free PMC article. - The Schizosaccharomyces pombe cdc5+ gene encodes an essential protein with homology to c-Myb.
Ohi R, McCollum D, Hirani B, Den Haese GJ, Zhang X, Burke JD, Turner K, Gould KL. Ohi R, et al. EMBO J. 1994 Jan 15;13(2):471-83. doi: 10.1002/j.1460-2075.1994.tb06282.x. EMBO J. 1994. PMID: 8313892 Free PMC article.
References
- Int J Pept Protein Res. 1983 Jul;22(1):1-15 - PubMed
- Nucleic Acids Res. 1990 Apr 11;18(7):1703-10 - PubMed
- Nature. 1986 Feb 13-19;319(6054):604-6 - PubMed
- Proc Natl Acad Sci U S A. 1986 May;83(10):3204-8 - PubMed
- Proc Natl Acad Sci U S A. 1986 Jul;83(14):5010-4 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources