Structural insights into the functions of TBK1 in innate antimicrobial immunity. | Academic Article individual record
abstract

Tank-binding kinase 1 (TBK1) is a serine/threonine protein-kinase mediating innate antimicrobial immunity. TBK1 is involved in the signaling of TLRs, RLRs, and STING-mediated sensing of cytosolic DNA. Stimulation of these receptors results in the activation of TBK1, which phosphorylates interferon regulatory factor (IRF)-3. Phosphorylated IRF-3 translocates into the nucleus to initiate the transcription of the interferon (IFN)-β gene. Here, we show that TBK1 is activated by autophosphorylation at residue Ser172. Structures of TBK1 bound to two inhibitors showed that TBK1 has the IκB kinase fold with three distinct domains: the kinase domain, the ubiquitin-like domain, and the scaffold and dimerization domain. However, the overall structures of the TBK1 monomer and its dimer are different from IKKβ in the arrangements of the three domains and in dimer formation. Phosphorylation of IRF-3 by TBK1 in vitro results in its oligomerization, and phosphorylation of residue Ser386 plays a key role in IRF-3 activation.

authors
author list (cited authors)
Shu, C., Sankaran, B., Chaton, C. T., Herr, A. B., Mishra, A., Peng, J., & Li, P.
publication date
2013
publisher
Elsevier BV Publisher
published in
Structure Journal
keywords
  • Humans
  • Indoles
  • Protein Multimerization
  • Structural Homology, Protein
  • Phosphorylation
  • Crystallography, X-Ray
  • Interferon Regulatory Factor-3
  • Enzyme Activation
  • Protein Structure, Secondary
  • Pyrroles
  • Molecular Sequence Data
  • Hydrophobic And Hydrophilic Interactions
  • Protein Structure, Quaternary
  • Protein Processing, Post-Translational
  • Hydrogen Bonding
  • Protein Interaction Domains And Motifs
  • Protein-Serine-Threonine Kinases
  • Animals
  • Models, Molecular
  • Amino Acid Sequence
  • Mice
  • Protein Kinase Inhibitors
  • Catalytic Domain
  • Bacterial Infections
  • Immunity, Innate
  • Protein Binding
altmetric score

0.75

citation count

57