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Bacterial lipids earmarked with ubiquitin for pathogen clearance
- Source :
- Nature
- Publication Year :
- 2021
-
Abstract
- Ubiquitylation, a wide-spread post-translational protein modification in eukaryotes, marks cytosol‐invading bacteria as cargo for anti-bacterial autophagy.(1–3) The identity of the ubiquitylated substrate on bacteria has remained unknown. Here we show that the ubiquitin coat on cytosol-invading Salmonella is formed through the unprecedented ubiquitylation of a non-proteinaceous substrate, the lipid A moiety of bacterial lipopolysaccharide (LPS), by the E3 ubiquitin ligase RNF213. RNF213 is a risk factor for Moyamoya disease (MMD)(4,5), a progressive stenosis of the supraclinoid internal carotid artery that causes stroke, especially in children.(6,7) RNF213 restricts the proliferation of cytosolic Salmonella and is essential for the generation of the bacterial ubiquitin coat, both directly, through ubiquitylation of LPS, and indirectly, through recruitment of LUBAC, a downstream E3 ligase that adds M1-linked ubiquitin chains onto pre-existing ubiquitin coats.(8) In cells lacking RNF213 bacteria do not attract ubiquitin-dependent autophagy cargo receptors and fail to induce anti-bacterial autophagy. The ubiquitylation of LPS on cytosol-invading Salmonella requires the dynein-like core of RNF213 but not its RING domain. Instead, LPS ubiquitylation relies on an RZ finger in the E3 shell. We conclude that ubiquitylation extends beyond protein substrates, that LPS ubiquitylation triggers cell-autonomous immunity and we postulate that non- proteinaceous substances other than LPS may also become ubiquitylated.
Details
- ISSN :
- 10974164
- Volume :
- 81
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Molecular cell
- Accession number :
- edsair.doi.dedup.....378d5cbea7bf0792818a1a2d9f7745ea