1SB0

Solution structure of the KIX domain of CBP bound to the transactivation domain of c-Myb

Summary for 1SB0

• Entry DOI: 10.2210/pdb1sb0/pdb
• NMR Information: BMRB: 6095
• Descriptor: protein CBP, protein c-Myb (2 entities in total)
• Functional Keywords: creb-binding protein; transcriptional activation; constitutive activation; lxxll motif; myb; kix, transcription
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cytoplasm (By similarity): P45481; Nucleus: P06876
• Total number of polymer chains: 2
• Total formula weight: 13301.33

Authors

Zor, T.,De Guzman, R.N.,Dyson, H.J.,Wright, P.E. (deposition date: 2004-02-09, release date: 2004-04-13, Last modification date: 2024-05-22)

Primary citation

Zor, T.,De Guzman, R.N.,Dyson, H.J.,Wright, P.E.
Solution Structure of the KIX Domain of CBP Bound to the Transactivation Domain of c-Myb
J.Mol.Biol., 337:521-534, 2004

PubMed Abstract: 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.

PubMed: 15019774
DOI: 10.1016/j.jmb.2004.01.038

Experimental method

SOLUTION NMR