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

Abstract

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.

• Authors: Kieron Brown, Sarah C M Vial, Neesha Dedi, Joanna M Long, Nicholas J Dunster, Graham M T Cheetham
• Journal: Journal of molecular biology (J Mol Biol) Vol. 354 Issue 5 Pg. 1013-20 (Dec 16 2005) ISSN: 0022-2836 [Print] Netherlands
• PMID: 16289117 (Publication Type: Journal Article)

Chemical References

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

Topics

• Adaptor Proteins, Signal Transducing (chemistry, genetics, isolation & purification, 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, metabolism)
• Mass Spectrometry
• Models, Molecular
• Molecular Sequence Data
• Protein Binding
• Protein Structure, Secondary
• Protein Structure, Tertiary
• Recombinant Fusion Proteins (chemistry, metabolism)
• Sequence Homology, Amino Acid
• Substrate Specificity