title: Solution structure of the KIX domain of CBP bound to the transactivation domain of CREB: a model for activator:coactivator interactions.
abstract: 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.
authors.affiliation: Department of Molecular Biology, and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: I
authors.initials: I
authors.lastname: Radhakrishnan
authors.forename: G C
authors.initials: GC
authors.lastname: Pérez-Alvarado
authors.forename: D
authors.initials: D
authors.lastname: Parker
authors.forename: H J
authors.initials: HJ
authors.lastname: Dyson
authors.forename: M R
authors.initials: MR
authors.lastname: Montminy
authors.forename: P E
authors.initials: PE
authors.lastname: Wright
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D050882:CREB-Binding Protein; D016384:Consensus Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000378:metabolism*; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D010748:Phosphopeptides; D015534:Trans-Activators; D014157:Transcription Factors; D050882:CREB-Binding Protein; C494363:CREBBP protein, human