Solution Structure of the KIX Domain of CBP Bound to the Transactivation Domain of c-Myb

摘要: The hematopoietic transcription factor c-Myb activates of target genes through direct interactions with the KIX domain co-activator CBP. solution structure in complex activation reveals a helical very similar to that adopted by phosphorylated kinase inducible (pKID) CREB. While pKID contains two helices, alphaA and alphaB, which interact KIX, bound single bent amphipathic helix binds same hydrophobic groove as alphaB pKID. affinity for is lower than pKID, relies more heavily on optimal residues groove. In particular, deep pocket accounts half observed NMR. A bend alpha-helix enables critical leucine side-chain penetrate into this deeply equivalent residue components mediate higher i.e. phosphate group helix, are absent from c-Myb. Results isothermal titration calorimetry, together structural data, point key difference between complexes pH binding, result differential pH-dependent histidine KIX. These results explain thermodynamic basis constitutive versus properties