Solution structure of the B-Myb DNA-binding domain: A possible role for conformational instability of the protein in DNA binding and control of gene expression

McIntosh, Pauline and Frenkiel, Tom A. and Wellborn, Ute and McCormick, John E. and Klempnauer, Karl-Heinz and Feeney, James and Carr, Mark D. (1998) Solution structure of the B-Myb DNA-binding domain: A possible role for conformational instability of the protein in DNA binding and control of gene expression. Biochemistry, 37 (27). pp. 9619-9629. ISSN 0006-2960. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1021/bi972861z

Abstract

Double- and triple-resonance heteronuclear NMR spectroscopy have been used to determine the high-resolution solution structure of the minimal B-Myb DNA-binding domain (B-MybR2R3) and to characterize the specific complex formed with a synthetic DNA fragment corresponding to the Myb target site on the Myb-regulated gene tom-1. B-MybR2R3 is shown to consist of two independent protein domains (R2 and R3) joined by a short linker, which have strikingly different tertiary structures despite significant sequence similarities, In addition, the C-terminal region of B-Myb R2 is confirmed to have a poorly defined structure, reflecting the existence of multiple conformations in slow to intermediate exchange. This contrasts with the tertiary structure reported for c-MybR2R3, in which both R2 and R3 have the same fold and the C-terminal region of R2 forms a stable, well-defined helix [Ogata, K., et al. (1995) Nat. Struct. Biol, 2, 309-320]. The NMR data suggest there are extensive contacts between B-MybR2R3 and its DNA target site in the complex and are consistent with a significant conformational change in the protein on binding to DNA, with one possibility being the formation of a stable helix in the C-terminal region of R2. In addition, conformational heterogeneity identified in R2 of B-MybR2R3 bound to the tom-1-A target site may play an important role in the control of gene expression by Myb proteins.

Item Type: Article
Additional information: his work was supported by the Medical Research Council (U.K.), the Department of Health (U.K.), and the Max-Planck Society (Germany). U.W. acknowledges the award of a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft. , ‡ The coordinates of the 32 converged B-MybR2R3 structures, together with the experimental NMR constraints, have been deposited in the Brookhaven Protein Data Bank (PDB file names 1a5j and r1a5jmr, respectively). , § National Institute for Biological Standards and Control. , MRC Biomedical NMR Centre, National Institute for Medical Research. , Division of Molecular Structure, National Institute for Medical Research. , # Max Planck Institut für Immunbiologie. , * To whom correspondence should be addressed at Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, U.K. , @ University of Kent.
Subjects: Q Science
Q Science > QD Chemistry
R Medicine
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: M.A. Ziai
Date Deposited: 22 Oct 2009 08:31
Last Modified: 18 Jun 2014 14:18
Resource URI: http://kar.kent.ac.uk/id/eprint/17447 (The current URI for this page, for reference purposes)
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