Leu628 of the KIX domain of CBP is a key residue for the interaction with the MLL transactivation domain

FEBS Lett. 2010 Nov 19;584(22):4500-4. doi: 10.1016/j.febslet.2010.10.024. Epub 2010 Oct 20.


Physical interaction between the transactivation domain (TAD) of the mixed-lineage leukemia protein (MLL) and the KIX domain of the cyclic-AMP response element binding protein (CREB) binding protein (CBP) is necessary for MLL-mediated transcriptional activation. We show by alanine-scanning mutagenesis that hydrophobic surface residues of KIX, especially L628, are energetically important for binding the MLL TAD. NMR studies of the KIX-L628A mutant suggest that L628 plays a crucial role in conformational transitions at the MLL binding site, necessary for high affinity interactions with MLL. Unexpectedly, MLL also binds to the c-Myb/phosphorylated kinase-inducible domain of CREB (pKID) site of KIX, highlighting the complex nature of interactions involving intrinsically disordered transcriptional activators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • CREB-Binding Protein / chemistry*
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism*
  • Humans
  • Leucine*
  • Mice
  • Models, Molecular
  • Mutagenesis
  • Mutation
  • Myeloid-Lymphoid Leukemia Protein / chemistry*
  • Myeloid-Lymphoid Leukemia Protein / genetics
  • Myeloid-Lymphoid Leukemia Protein / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Structure, Tertiary
  • Transcriptional Activation*


  • Myeloid-Lymphoid Leukemia Protein
  • CREB-Binding Protein
  • Leucine