Structural highlights
Publication Abstract from PubMedTank-binding kinase I (TBK1) plays a key role in the innate immune system by integrating signals from pattern-recognition receptors. Here, we report the X-ray crystal structures of inhibitor-bound inactive and active TBK1 determined to 2.6 A and 4.0 A resolution, respectively. The structures reveal a compact dimer made up of trimodular subunits containing an N-terminal kinase domain (KD), a ubiquitin-like domain (ULD), and an alpha-helical scaffold dimerization domain (SDD). Activation rearranges the KD into an active conformation while maintaining the overall dimer conformation. Low-resolution SAXS studies reveal that the missing C-terminal domain (CTD) extends away from the main body of the kinase dimer. Mutants that interfere with TBK1 dimerization show significantly reduced trans-autophosphorylation but retain the ability to bind adaptor proteins through the CTD. Our results provide detailed insights into the architecture of TBK1 and the molecular mechanism of activation. Crystal structure and mechanism of activation of TANK-binding kinase 1.,Larabi A, Devos JM, Ng SL, Nanao MH, Round A, Maniatis T, Panne D Cell Rep. 2013 Mar 28;3(3):734-46. doi: 10.1016/j.celrep.2013.01.034. Epub 2013, Feb 28. PMID:23453971[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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