8ik0

Structural highlights

Function

TSI3_PSEAE Immunity protein that plays a role in preventing early activation of toxin Tse3. Occupies Tse3 substrate binding site and prevents the substrate from entering.^{[1] [2]} STING_CHICK 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) (By similarity). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (By similarity). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:30842659). Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes and 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 (PubMed:30842659). In addition to promote the production of type I interferons, plays a direct role in autophagy (By similarity). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By similarity). The ERGIC serves as the membrane source for LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (By similarity). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (By similarity). Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (By similarity).[UniProtKB:Q86WV6]^[3]

References

1. ↑ Li L, Zhang W, Liu Q, Gao Y, Gao Y, Wang Y, Wang DZ, Li Z, Wang T. Structural Insights on the Bacteriolytic and Self-protection Mechanism of Muramidase Effector Tse3 in Pseudomonas aeruginosa. J Biol Chem. 2013 Oct 18;288(42):30607-13. doi: 10.1074/jbc.C113.506097. Epub, 2013 Sep 11. PMID:24025333 doi:http://dx.doi.org/10.1074/jbc.C113.506097
2. ↑ Lu D, Shang G, Zhang H, Yu Q, Cong X, Yuan J, He F, Zhu C, Zhao Y, Yin K, Chen Y, Hu J, Zhang X, Yuan Z, Xu S, Hu W, Cang H, Gu L. Structural insights into the T6SS effector protein Tse3 and the Tse3-Tsi3 complex from Pseudomonas aeruginosa reveal a calcium-dependent membrane-binding mechanism. Mol Microbiol. 2014 Apr 14. doi: 10.1111/mmi.12616. PMID:24724564 doi:http://dx.doi.org/10.1111/mmi.12616
3. ↑ Shang G, Zhang C, Chen ZJ, Bai XC, Zhang X. Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP. Nature. 2019 Mar 6. pii: 10.1038/s41586-019-0998-5. doi:, 10.1038/s41586-019-0998-5. PMID:30842659 doi:http://dx.doi.org/10.1038/s41586-019-0998-5