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

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 alpha B of pKID interacts with a hydrophobic groove defined by helices alpha 1 and alpha 3 of KIX. The other pKID helix, alpha A, contacts a different face of the alpha 3 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.