The KIX domain of the transcriptional co-activator CBP co-operatively mediates interactions between transcription factors. Binding of the transcription factor MLL induces the formation of a low-populated conformer of KIX that resembles the conformation of the KIX domain in the presence of a second transcription factor molecule. NMR spin relaxation studies have previously showed that allosteric coupling proceeds through a network of hydrophobic core residues that bridge the two binding sites. Here we describe high-resolution NMR solution structures of the binary complex of KIX with MLL and the ternary complex of KIX formed with MLL and pKID as a second ligand. We show that binding of pKID to the binary complex of KIX with MLL is accompanied by a defined re-packing of the allosteric network in the hydrophobic core of the protein. Rotamer populations derived from methyl group 13C chemical shifts reveal a dynamic contribution to the re-packing process that is not captured by the structural coordinates and exemplify the dynamic nature of allosteric communication in the KIX domain.