title: Allosteric communication in the KIX domain proceeds through dynamic repacking of the hydrophobic core.
abstract: The KIX domain of the transcriptional coactivator CREB binding protein (CBP) co-operatively mediates interactions between transcription factors. Binding of the transcription factor mixed-lineage leukemia (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 shown 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 phosphorylated kinase inducible domain of CREB (pKID) as a second ligand. We show that binding of pKID to the binary complex of KIX with MLL is accompanied by a defined repacking of the allosteric network in the hydrophobic core of the protein. Rotamer populations derived from methyl group (13)C chemical shifts reveal a dynamic contribution to the repacking process that is not captured by the structural coordinates and exemplify the dynamic nature of allosteric communication in the KIX domain.
authors: Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck , Innrain 80/82, A-6020 Innsbruck, Austria.
authors: Sven
authors: S
authors: Brüschweiler
authors: Robert
authors: R
authors: Konrat
authors: Martin
authors: M
authors: Tollinger
mesh_terms: D000494:Allosteric Regulation; D050882:CREB-Binding Protein / Q000502:physiology*; D056831:Coordination Complexes / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D008968:Molecular Conformation; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D056831:Coordination Complexes; D050882:CREB-Binding Protein
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