ArticleProceedings of the National Academy of Sciences of the United States of America2022
Mechanistic insights into the subversion of the linear ubiquitin chain assembly complex by the E3 ligase IpaH1.4 of
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Manipulation of nonclassical ubiquitin signaling by pathogenic bacteria.Current opinion in microbiology · 2026Review
- Article
- Covalent fragment screening to inhibit the E3 ligase activity of bacterial NEL enzymes SspH1 and SspH2.RSC chemical biology · 2026Article
- TheeLife · 2025Article
- Shigella flexneri evades LPS ubiquitylation through IpaH1.4-mediated degradation of RNF213.Nature structural & molecular biology · 2025Article
- ThebioRxiv : the preprint server for biology · 2025Article
- Shigella effector IpaH1.4 subverts host E3 ligase RNF213 to evade antibacterial immunity.Nature communications · 2025Article
- Staphylococcal SplA and SplB serine proteases target ubiquitin(-like) specific proteases.AMB Express · 2025Article
- Mechanistic insights into the enzymatic activity of E3 ligase HOIL-1L and its regulation by the linear ubiquitin chain binding.Science advances · 2023Article
- Ubiquitin-targeted bacterial effectors: rule breakers of the ubiquitin system.The EMBO journal · 2023Review
- Article
- Ubiquitin and its relatives as wizards of the endolysosomal system.Journal of cell science · 2023Article
- The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family.Nature communications · 2023Article
- The NEL Family of Bacterial E3 Ubiquitin Ligases.International journal of molecular sciences · 2022Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Shigella flexneri, a gram-negative bacterium, is the major culprit of bacterial shigellosis and causes a large number of human infection cases and deaths worldwide annually. For evading the host immune response during infection, S. flexneri secrets two highly similar E3 ligases, IpaH1.4 and IpaH2.5, to subvert the linear ubiquitin chain assembly complex (LUBAC) of host cells, which is composed of HOIP, HOIL-1L, and SHARPIN. However, the detailed molecular mechanism underpinning the subversion of the LUBAC by IpaH1.4/2.5 remains elusive. Here, we demonstrated that IpaH1.4 can specifically recognize HOIP and HOIL-1L through its leucine-rich repeat (LRR) domain by binding to the HOIP RING1 domain and HOIL-1L ubiquitin-like (UBL) domain, respectively. The determined crystal structures of IpaH1.4 LRR/HOIP RING1, IpaH1.4 LRR/HOIL-1L UBL, and HOIP RING1/UBE2L3 complexes not only elucidate the binding mechanisms of IpaH1.4 with HOIP and HOIL-1L but also unveil that the recognition of HOIP by IpaH1.4 can inhibit the E2 binding of HOIP. Furthermore, we demonstrated that the interaction of IpaH1.4 LRR with HOIP RING1 or HOIL-1L UBL is essential for the ubiquitination of HOIP or HOIL-1L in vitro as well as the suppression of NF-κB activation by IpaH1.4 in cells. In summary, our work elucidated that in addition to inducing the proteasomal degradation of LUBAC, IpaH1.4 can also inhibit the E3 activity of LUBAC by blocking its E2 loading and/or disturbing its stability, thereby providing a paradigm showing how a bacterial E3 ligase adopts multiple tactics to subvert the key LUBAC of host cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.