Principles of protein-DNA recognition revealed in the structural analysis of Ndt80-MSE DNA complexes

Structure. 2006 Mar;14(3):555-65. doi: 10.1016/j.str.2005.11.017.


The Saccharomyces cerevisiae transcription factor Ndt80 selectively binds a DNA consensus sequence (the middle sporulation element [MSE]) to activate gene expression after the successful completion of meiotic recombination. Here we report the X-ray crystal structures of Ndt80 bound to ten distinct MSE variants. Comparison of these structures with the structure of Ndt80 bound to a consensus MSE reveals structural principles that determine the DNA binding specificity of this transcription factor. The 5' GC-rich end of the MSE contains distinct 5'-YpG-3' steps that are recognized by arginine side chains through a combination of hydrogen bonding and cation-pi interactions. The 3' AT-rich region is recognized via minor groove contacts that sterically exclude the N2 atom of GC base pairs. The conformation of the AT-rich region is fixed by interactions with the protein that favor recognition of poly(A)-poly(T) versus mixed AT sequences through an avoidance of major groove steric clashes at 5'-ApT-3' steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Composition
  • Base Pairing
  • Base Sequence
  • Consensus Sequence
  • Crystallography, X-Ray
  • DNA / chemistry*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation, Fungal
  • Genetic Variation
  • Hydrogen Bonding
  • Models, Molecular
  • Molecular Sequence Data
  • Mutant Proteins / chemistry
  • Protein Conformation
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*
  • Structure-Activity Relationship
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Mutant Proteins
  • NDT80 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • DNA

Associated data

  • PDB/2ETW
  • PDB/2EUV
  • PDB/2EUW
  • PDB/2EUX
  • PDB/2EUZ
  • PDB/2EVF
  • PDB/2EVG
  • PDB/2EVH
  • PDB/2EVI
  • PDB/2EVJ