Structural basis for the interaction of TAK1 kinase with its activating protein TAB1

J Mol Biol. 2005 Dec 16;354(5):1013-20. doi: 10.1016/j.jmb.2005.09.098. Epub 2005 Nov 2.


Transforming growth factor-beta (TGF-beta)-activated kinase 1 (TAK1) is a member of the MAPKKK family of protein kinases, and is involved in intracellular signalling pathways stimulated by transforming growth factor beta, interleukin-1 and tumour necrosis factor-alpha. TAK1 is known to rely upon an additional protein, TAK1-binding protein 1 (TAB1), for complete activation. However, the molecular basis for this activation has yet to be elucidated. We have solved the crystal structure of a novel TAK1 chimeric protein and these data give insight into how TAK1 is activated by TAB1. Our results reveal a novel binding pocket on the TAK1 kinase domain whose shape complements that of a unique alpha-helix in the TAK1 binding domain of TAB1, providing the basis for an intimate hydrophobic association between the protein activator and its target.

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry*
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / isolation & purification
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adenosine / metabolism
  • Amino Acid Sequence
  • Baculoviridae / genetics
  • Binding Sites
  • Crystallography, X-Ray
  • Enzyme Activation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • MAP Kinase Kinase Kinases / chemistry*
  • MAP Kinase Kinase Kinases / metabolism*
  • Mass Spectrometry
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity


  • Adaptor Proteins, Signal Transducing
  • Recombinant Fusion Proteins
  • TAB1 protein, human
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7
  • Adenosine

Associated data

  • PDB/2EVA