1sb0
From Proteopedia
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Solution structure of the KIX domain of CBP bound to the transactivation domain of c-Myb
Overview
The hematopoietic transcription factor c-Myb activates transcription of, target genes through direct interactions with the KIX domain of the, co-activator CBP. The solution structure of the KIX domain in complex with, the activation domain of c-Myb reveals a helical structure very similar to, that adopted by KIX in complex with the phosphorylated kinase inducible, domain (pKID) of CREB. While pKID contains two helices, alphaA and alphaB, which interact with KIX, the structure of bound c-Myb reveals a single, bent amphipathic helix that binds in the same hydrophobic groove as the, alphaB helix of pKID. The affinity of c-Myb for KIX is lower than that of, pKID, and relies more heavily on optimal interactions of the single helix, of c-Myb with residues in the hydrophobic groove. In particular, a deep, hydrophobic pocket in KIX accounts for more than half the interactions, with c-Myb observed by NMR. A bend in the alpha-helix of c-Myb enables a, critical leucine side-chain to penetrate into this pocket more deeply than, the equivalent leucine residue of pKID. The components that mediate the, higher affinity of pKID for KIX, i.e. the phosphate group and the alphaA, helix, are absent from c-Myb. Results from isothermal titration, calorimetry, together with the structural data, point to a key difference, between the two complexes in optimal pH for binding, as a result of, differential pH-dependent interactions with histidine residues of KIX., These results explain the structural and thermodynamic basis for the, observed constitutive versus inducible activation properties of c-Myb and, CREB.
About this Structure
1SB0 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
Reference
Solution structure of the KIX domain of CBP bound to the transactivation domain of c-Myb., Zor T, De Guzman RN, Dyson HJ, Wright PE, J Mol Biol. 2004 Mar 26;337(3):521-34. PMID:15019774
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