7wr4

Structural highlights

Function

OSPC3_SHIFL ADP-riboxanase effector that inhibits host cell pyroptosis (PubMed:23684308, PubMed:34409271, PubMed:34671164). Acts by mediating arginine ADP-riboxanation of host CASP4/CASP11, blocking CASP4/CASP11 autoprocessing (PubMed:34671164, PubMed:35338844, PubMed:35568036). This prevents CASP4 activation and ability to recognize and cleave GSDMD, thereby inhibiting LPS-induced pyroptosis (PubMed:34671164). ADP-riboxanation takes place in two steps: OspC3 first catalyzes ADP-ribosylation of target Arg, and then initiates a deamination to remove one N-omega group (PubMed:34671164). Independently of its ADP-riboxanase activity, acts as an inhibitor of calcium signaling by inhibiting host calmodulin, preventing activation of the JAK-STAT signaling pathway in response to interferon-beta (PubMed:35568036). Mechanistically, acts by binding to the apo form of calmodulin, preventing calcium-binding and ability to activate host CaMK2 (CAMKII), which is required to stimulate the JAK-STAT signaling pathway in response to interferon-beta (PubMed:35568036).^{[1] [2] [3] [4] [5]}

References

1. ↑ Kobayashi T, Ogawa M, Sanada T, Mimuro H, Kim M, Ashida H, Akakura R, Yoshida M, Kawalec M, Reichhart JM, Mizushima T, Sasakawa C. The Shigella OspC3 effector inhibits caspase-4, antagonizes inflammatory cell death, and promotes epithelial infection. Cell Host Microbe. 2013 May 15;13(5):570-583. doi: 10.1016/j.chom.2013.04.012. PMID:23684308 doi:http://dx.doi.org/10.1016/j.chom.2013.04.012
2. ↑ Oh C, Verma A, Hafeez M, Hogland B, Aachoui Y. Shigella OspC3 suppresses murine cytosolic LPS sensing. iScience. 2021 Jul 28;24(8):102910. doi: 10.1016/j.isci.2021.102910. eCollection , 2021 Aug 20. PMID:34409271 doi:http://dx.doi.org/10.1016/j.isci.2021.102910
3. ↑ Li Z, Liu W, Fu J, Cheng S, Xu Y, Wang Z, Liu X, Shi X, Liu Y, Qi X, Liu X, Ding J, Shao F. Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11. Nature. 2021 Nov;599(7884):290-295. doi: 10.1038/s41586-021-04020-1. Epub 2021, Oct 20. PMID:34671164 doi:http://dx.doi.org/10.1038/s41586-021-04020-1
4. ↑ Peng T, Tao X, Xia Z, Hu S, Xue J, Zhu Q, Pan X, Zhang Q, Li S. Pathogen hijacks programmed cell death signaling by arginine ADPR-deacylization of caspases. Mol Cell. 2022 May 19;82(10):1806-1820.e8. doi: 10.1016/j.molcel.2022.03.010. , Epub 2022 Mar 25. PMID:35338844 doi:http://dx.doi.org/10.1016/j.molcel.2022.03.010
5. ↑ Alphonse N, Wanford JJ, Voak AA, Gay J, Venkhaya S, Burroughs O, Mathew S, Lee T, Evans SL, Zhao W, Frowde K, Alrehaili A, Dickenson RE, Munk M, Panina S, Mahmood IF, Llorian M, Stanifer ML, Boulant S, Berchtold MW, Bergeron JRC, Wack A, Lesser CF, Odendall C. A family of conserved bacterial virulence factors dampens interferon responses by blocking calcium signaling. Cell. 2022 Jun 23;185(13):2354-2369.e17. doi: 10.1016/j.cell.2022.04.028. Epub , 2022 May 13. PMID:35568036 doi:http://dx.doi.org/10.1016/j.cell.2022.04.028