4jlc
Crystal structure of mouse TBK1 bound to SU6668Crystal structure of mouse TBK1 bound to SU6668
Template:ABSTRACT PUBMED 23746807
FunctionFunction
[TBK1_MOUSE] Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFN-alpha and IFN-beta. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS or SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating IKKA/CHUK or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser-177', thus enhancing LC3 binding affinity and antibacterial autophagy. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates and activates AKT1 (By similarity).[1] [2]
About this StructureAbout this Structure
4jlc is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
- ↑ Shu C, Sankaran B, Chaton CT, Herr AB, Mishra A, Peng J, Li P. Structural Insights into the Functions of TBK1 in Innate Antimicrobial Immunity. Structure. 2013 Jun 5. pii: S0969-2126(13)00155-X. doi:, 10.1016/j.str.2013.04.025. PMID:23746807 doi:10.1016/j.str.2013.04.025
- ↑ Pomerantz JL, Baltimore D. NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J. 1999 Dec 1;18(23):6694-704. PMID:10581243 doi:10.1093/emboj/18.23.6694
- ↑ O'Connell RM, Vaidya SA, Perry AK, Saha SK, Dempsey PW, Cheng G. Immune activation of type I IFNs by Listeria monocytogenes occurs independently of TLR4, TLR2, and receptor interacting protein 2 but involves TNFR-associated NF kappa B kinase-binding kinase 1. J Immunol. 2005 Feb 1;174(3):1602-7. PMID:15661922