| Structural highlights
Function
IPA14_SHIFL E3 ubiquitin-protein ligase effector that inhibits host cell innate immunity during bacterial infection by catalyzing 'Lys-48'-linked polyubiquitination and subsequent degradation of host RNF31/HOIP (PubMed:27572974). Host RNF31/HOIP is the catalytic component of the LUBAC complex, which conjugates linear ('Met-1'-linked) polyubiquitin chains at the surface of bacteria invading the host cytosol to form the ubiquitin coat surrounding bacteria (PubMed:27572974). The bacterial ubiquitin coat acts as an 'eat-me' signal for xenophagy and promotes NF-kappa-B activation (PubMed:27572974, PubMed:28481331). By promoting degradation of host RNF31/HOIP, IpaH1.4 prevents formation of the bacterial ubiquitin coat and activation of host cell innate immunity (PubMed:27572974, PubMed:28481331).[1] [2]
Publication Abstract from PubMed
SignificanceShigella flexneri, a deleterious bacterium, causes massive human infection cases and deaths worldwide. To facilitate survival and replication in infected host cells, S. flexneri can secrete two highly similar E3 ligase effectors, IpaH1.4 and IpaH2.5, to subvert the linear ubiquitin chain assembly complex (LUBAC), a key player involved in numerous antibacterial signaling pathways of host cells but with poorly understood mechanisms. In this study, through systematic biochemical and structural characterization, we elucidate the multiple tactics adopted by IpaH1.4/2.5 to disarm the human LUBAC and provide mechanistic insights into the subversion of host LUBAC by IpaH1.4/2.5 of S. flexneri.
Mechanistic insights into the subversion of the linear ubiquitin chain assembly complex by the E3 ligase IpaH1.4 of Shigella flexneri.,Liu J, Wang Y, Wang D, Wang Y, Xu X, Zhang Y, Li Y, Zhang M, Gong X, Tang Y, Shen L, Li M, Pan L Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2116776119. doi:, 10.1073/pnas.2116776119. Epub 2022 Mar 16. PMID:35294289[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ de Jong MF, Liu Z, Chen D, Alto NM. Shigella flexneri suppresses NF-κB activation by inhibiting linear ubiquitin chain ligation. Nat Microbiol. 2016 May 27;1(7):16084. PMID:27572974 doi:10.1038/nmicrobiol.2016.84
- ↑ Noad J, von der Malsburg A, Pathe C, Michel MA, Komander D, Randow F. LUBAC-synthesized linear ubiquitin chains restrict cytosol-invading bacteria by activating autophagy and NF-κB. Nat Microbiol. 2017 May 8;2:17063. PMID:28481331 doi:10.1038/nmicrobiol.2017.63
- ↑ Liu J, Wang Y, Wang D, Wang Y, Xu X, Zhang Y, Li Y, Zhang M, Gong X, Tang Y, Shen L, Li M, Pan L. Mechanistic insights into the subversion of the linear ubiquitin chain assembly complex by the E3 ligase IpaH1.4 of Shigella flexneri. Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2116776119. PMID:35294289 doi:10.1073/pnas.2116776119
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