Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions

Cell. 1997 Dec 12;91(6):741-52. doi: 10.1016/s0092-8674(00)80463-8.


The nuclear factor CREB activates transcription of target genes in part through direct interactions with the KIX domain of the coactivator CBP in a phosphorylation-dependent manner. The solution structure of the complex formed by the phosphorylated kinase-inducible domain (pKID) of CREB with KIX reveals that pKID undergoes a coil-->helix folding transition upon binding to KIX, forming two alpha helices. The amphipathic helix alphaB of pKID interacts with a hydrophobic groove defined by helices alpha1 and alpha3 of KIX. The other pKID helix, alphaA, contacts a different face of the alpha3 helix. The phosphate group of the critical phosphoserine residue of pKID forms a hydrogen bond to the side chain of Tyr-658 of KIX. The structure provides a model for interactions between other transactivation domains and their targets.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CREB-Binding Protein
  • Consensus Sequence
  • Cyclic AMP Response Element-Binding Protein / chemistry*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Nuclear Proteins / metabolism*
  • Phosphopeptides / chemistry
  • Phosphopeptides / metabolism
  • Protein Conformation*
  • Protein Structure, Secondary
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Trans-Activators*
  • Transcription Factors / metabolism*


  • Cyclic AMP Response Element-Binding Protein
  • Nuclear Proteins
  • Phosphopeptides
  • Trans-Activators
  • Transcription Factors
  • CREB-Binding Protein
  • CREBBP protein, human

Associated data

  • PDB/1KDX