4JLC

Crystal structure of mouse TBK1 bound to SU6668

Summary for 4JLC

• Entry DOI: 10.2210/pdb4jlc/pdb
• Related: 4JL9
• Descriptor: Serine/threonine-protein kinase TBK1, 3-{2,4-dimethyl-5-[(Z)-(2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl}propanoic acid (2 entities in total)
• Functional Keywords: protein kinase, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Mus musculus (mouse)
• Cellular location: Cytoplasm: Q9WUN2
• Total number of polymer chains: 1
• Total formula weight: 76000.72

Authors

Li, P. (deposition date: 2013-03-12, release date: 2013-06-19, Last modification date: 2023-09-20)

Primary citation

Shu, C.,Sankaran, B.,Chaton, C.T.,Herr, A.B.,Mishra, A.,Peng, J.,Li, P.
Structural Insights into the Functions of TBK1 in Innate Antimicrobial Immunity.
Structure, 21:1137-1148, 2013

PubMed 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.

PubMed: 23746807
DOI: 10.1016/j.str.2013.04.025

Experimental method

X-RAY DIFFRACTION (3 Å)