NMR structure of the DNA-binding domain of the cell cycle protein Mbp1 from Saccharomyces cerevisiae

Biochemistry. 2003 Feb 11;42(5):1266-73. doi: 10.1021/bi0205247.

Abstract

The three-dimensional solution structure of the DNA-binding domain of Mlu-1 box binding protein (Mbp1) has been determined by multidimensional NMR spectroscopy. Mbp1 is a cell cycle transcription factor from Saccharomyces cerevisiae and consists of an N-terminal DNA-binding domain, a series of ankyrin repeats, and a heterodimerization domain at the C-terminus. A set of conformers comprising 19 refined structures was calculated via a molecular dynamics simulated annealing protocol using distance, dihedral angle, and residual dipolar coupling restraints derived from either double or triple resonance NMR experiments. The solution structure consists of a six-stranded beta-sheet segment folded against two pairs of alpha-helices in the topology of the winged helix-turn-helix family of proteins and is in agreement with the X-ray structures. In addition, the solution structure shows that the C-terminal tail region of this domain folds back and makes specific interactions with the N-terminal beta-strand of the protein. This C-terminal region is essential for full DNA-binding activity but appears in the X-ray structure to be disordered. The fold-back structure extends the region of positive electrostatic potential, and this may enhance the nonspecific contribution to binding by favorable electrostatic interactions with the DNA backbone.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Cycle Proteins / chemistry*
  • Computer Simulation
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry*
  • Helix-Turn-Helix Motifs
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular* / methods
  • Peptide Fragments / chemistry
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Lösungen
  • Static Electricity
  • Thermodynamics
  • Transcription Factors / chemistry*

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MBP1 protein, S cerevisiae
  • Peptide Fragments
  • Saccharomyces cerevisiae Proteins
  • Lösungen
  • Transcription Factors