Proteopedia

6o8c

Revision as of 09:55, 23 May 2019 by OCA (talk | contribs)

Crystal structure of STING CTT in complex with TBK1Crystal structure of STING CTT in complex with TBK1

Structural highlights

6o8c is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Activity:Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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] [STING_HUMAN] Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway.[3] [4] [5] [6] [7] [8] [9]

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Zhong B, Yang Y, Li S, Wang YY, Li Y, Diao F, Lei C, He X, Zhang L, Tien P, Shu HB. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity. 2008 Oct 17;29(4):538-50. doi: 10.1016/j.immuni.2008.09.003. Epub 2008 , Sep 25. PMID:18818105 doi:10.1016/j.immuni.2008.09.003
  4. ↑ Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008 Oct 2;455(7213):674-8. doi: 10.1038/nature07317. Epub 2008 Aug 24. PMID:18724357 doi:10.1038/nature07317
  5. ↑ Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature. 2009 Oct 8;461(7265):788-92. doi: 10.1038/nature08476. Epub 2009 Sep 23. PMID:19776740 doi:10.1038/nature08476
  6. ↑ Sun W, Li Y, Chen L, Chen H, You F, Zhou X, Zhou Y, Zhai Z, Chen D, Jiang Z. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proc Natl Acad Sci U S A. 2009 May 26;106(21):8653-8. doi:, 10.1073/pnas.0900850106. Epub 2009 May 11. PMID:19433799 doi:10.1073/pnas.0900850106
  7. ↑ Tsuchida T, Zou J, Saitoh T, Kumar H, Abe T, Matsuura Y, Kawai T, Akira S. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity. 2010 Nov 24;33(5):765-76. doi: 10.1016/j.immuni.2010.10.013. Epub 2010 , Nov 11. PMID:21074459 doi:10.1016/j.immuni.2010.10.013
  8. ↑ Burdette DL, Monroe KM, Sotelo-Troha K, Iwig JS, Eckert B, Hyodo M, Hayakawa Y, Vance RE. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 2011 Sep 25;478(7370):515-8. doi: 10.1038/nature10429. PMID:21947006 doi:10.1038/nature10429
  9. ↑ Wu J, Sun L, Chen X, Du F, Shi H, Chen C, Chen ZJ. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013 Feb 15;339(6121):826-30. doi: 10.1126/science.1229963. Epub 2012, Dec 20. PMID:23258412 doi:10.1126/science.1229963

6o8c, resolution 3.17Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=6o8c&oldid=3046392"