8efp

Structural highlights

Function

IPA7_SHIFL E3 ubiquitin ligase effector protein that interferes with host's innate immunity (PubMed:30872533, PubMed:34022140, PubMed:34492225, PubMed:36599845, PubMed:36991122, PubMed:36991125). Functions to alter host cell physiology and promote bacterial survival in host tissues (PubMed:30872533, PubMed:34022140, PubMed:34492225). Catalyzes ubiquitination of human gasdermins GSDMB and GSDMD, promoting their degradation by the proteasome, thereby preventing cell death (PubMed:34022140, PubMed:34492225, PubMed:36599845, PubMed:36991122, PubMed:36991125). In contrast, activates host cell pyroptosis in mouse cells: catalyzes ubiquitination of mouse Nlrp1b allele 1 protein, releasing the cleaved C-terminal part of Nlrp1b, which polymerizes and forms the Nlrp1b inflammasome followed by host cell pyroptosis (PubMed:30872533). Does not catalyze ubiquitination of mouse GSDMD (PubMed:36599845, PubMed:36991122, PubMed:36991125).^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Sandstrom A, Mitchell PS, Goers L, Mu EW, Lesser CF, Vance RE. Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes. Science. 2019 Apr 5;364(6435):eaau1330. doi: 10.1126/science.aau1330. Epub 2019 , Mar 14. PMID:30872533 doi:http://dx.doi.org/10.1126/science.aau1330
2. ↑ Hansen JM, de Jong MF, Wu Q, Zhang LS, Heisler DB, Alto LT, Alto NM. Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions. Cell. 2021 Jun 10;184(12):3178-3191.e18. PMID:34022140 doi:10.1016/j.cell.2021.04.036
3. ↑ Luchetti G, Roncaioli JL, Chavez RA, Schubert AF, Kofoed EM, Reja R, Cheung TK, Liang Y, Webster JD, Lehoux I, Skippington E, Reeder J, Haley B, Tan MW, Rose CM, Newton K, Kayagaki N, Vance RE, Dixit VM. Shigella ubiquitin ligase IpaH7.8 targets gasdermin D for degradation to prevent pyroptosis and enable infection. Cell Host Microbe. 2021 Oct 13;29(10):1521-1530.e10. PMID:34492225 doi:10.1016/j.chom.2021.08.010
4. ↑ Yin H, Zheng J, He Q, Zhang X, Li X, Ma Y, Liang X, Gao J, Kocsis BL, Li Z, Liu X, Alto NM, Li L, Zhang H. Insights into the GSDMB-mediated cellular lysis and its targeting by IpaH7.8. Nat Commun. 2023 Jan 4;14(1):61. PMID:36599845 doi:10.1038/s41467-022-35725-0
5. ↑ Wang C, Shivcharan S, Tian T, Wright S, Ma D, Chang J, Li K, Song K, Xu C, Rathinam VA, Ruan J. Structural basis for GSDMB pore formation and its targeting by IpaH7.8. Nature. 2023 Apr;616(7957):590-597. PMID:36991122 doi:10.1038/s41586-023-05832-z
6. ↑ Zhong X, Zeng H, Zhou Z, Su Y, Cheng H, Hou Y, She Y, Feng N, Wang J, Shao F, Ding J. Structural mechanisms for regulation of GSDMB pore-forming activity. Nature. 2023 Mar 29. PMID:36991125 doi:10.1038/s41586-023-05872-5