7v8e

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]}

References

1. ↑ 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
2. ↑ 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
3. ↑ 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