Nucleic Acids Research, Vol 24, Issue 20 3990-3995, Copyright © 1996 by Oxford University Press
AB Hegvold and OS Gabrielsen
The DNA-binding domain of the oncoprotein c-Myb consists of three imperfect
tryptophan-rich repeats, R1, R2 and R3. Each repeat forms an independent
mini-domain with a helix-turn-helix related motif and they are connected by
linkers containing highly conserved residues. The location of the linker
between two DNA-binding units suggests a function analogous to a
dimerisation motif with a critical role in positioning the recognition
helices of each mini-domain. Mutational analysis of the minimal DNA-binding
domain of chicken c-Myb (R2 and R3), revealed that besides the recognition
helices of each repeat, the linker connecting them was of critical
importance in maintaining specific DNA-binding. A comparison of several
linker sequences from different Myb proteins revealed a highly conserved
motif of four amino acids in the first half of the linker: LNPE (L138 to
E141 in chicken c- Myb R2R3). Substitution of residues within this sequence
led to reduced stability of protein-DNA complexes and even loss of
DNA-binding. The two most affected mutants showed increased accessibility
to proteases, and fluorescence emission spectra and quenching experiments
revealed greater average exposure of tryptophans which suggests changes in
conformation of the proteins. From the structure of R2R3 we propose that
the LNPE motif provides two functions: anchorage to the first repeat
(through L) and determination of the direction of the bridge to the next
repeat (through P).
ARTICLES
The importance of the linker connecting the repeats of the c-Myb oncoprotein may be due to a positioning function
Department of Biochemistry, University of Oslo, Norway.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. A. Krizek AINTEGUMENTA utilizes a mode of DNA recognition distinct from that used by proteins containing a single AP2 domain Nucleic Acids Res., April 1, 2003; 31(7): 1859 - 1868. [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]
|
|
|
|
 |
|
 E. Grotewold, M. B. Sainz, L. Tagliani, J. M. Hernandez, B. Bowen, and V. L. Chandler Identification of the residues in the Myb domain of maize C1 that specify the interaction with the bHLH cofactor R PNAS, November 22, 2000; (2000) 250379897. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. D. Rabinowicz, E. L. Braun, A. D. Wolfe, B. Bowen, and E. Grotewold Maize R2R3 Myb Genes: Sequence Analysis Reveals Amplification in the Higher Plants Genetics, September 1, 1999; 153(1): 427 - 444. [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]
|
|
|
|
|
|
E. Grotewold, M. B. Sainz, L. Tagliani, J. M. Hernandez, B. Bowen, and V. L. Chandler Identification of the residues in the Myb domain of maize C1 that specify the interaction with the bHLH cofactor R PNAS, December 5, 2000; 97(25): 13579 - 13584. [Abstract] [Full Text] [PDF]
|
|