Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection

Elsje G. Otten (), Emma Werner, Ana Crespillo-Casado, Keith B. Boyle, Vimisha Dharamdasani, Claudio Pathe, Balaji Santhanam and Felix Randow ()
Additional contact information
Elsje G. Otten: MRC Laboratory of Molecular Biology
Emma Werner: MRC Laboratory of Molecular Biology
Ana Crespillo-Casado: MRC Laboratory of Molecular Biology
Keith B. Boyle: MRC Laboratory of Molecular Biology
Vimisha Dharamdasani: MRC Laboratory of Molecular Biology
Claudio Pathe: MRC Laboratory of Molecular Biology
Balaji Santhanam: MRC Laboratory of Molecular Biology
Felix Randow: MRC Laboratory of Molecular Biology

Nature, 2021, vol. 594, issue 7861, 111-116

Abstract: Abstract Ubiquitylation is a widespread post-translational protein modification in eukaryotes and marks bacteria that invade the cytosol as cargo for antibacterial autophagy1–3. The identity of the ubiquitylated substrate on bacteria is unknown. Here we show that the ubiquitin coat on Salmonella that invade the cytosol is formed through the ubiquitylation of a non-proteinaceous substrate, the lipid A moiety of bacterial lipopolysaccharide (LPS), by the E3 ubiquitin ligase ring finger protein 213 (RNF213). RNF213 is a risk factor for moyamoya disease4,5, which is 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 the ubiquitylation of LPS) and indirectly (through the recruitment of LUBAC, which is a downstream E3 ligase that adds M1-linked ubiquitin chains onto pre-existing ubiquitin coats8). In cells that lack RNF213, bacteria do not attract ubiquitin-dependent autophagy receptors or induce antibacterial autophagy. The ubiquitylation of LPS on Salmonella that invade the cytosol requires the dynein-like core of RNF213, but not its RING domain. Instead, ubiquitylation of LPS relies on an RZ finger in the E3 shell. We conclude that ubiquitylation extends beyond protein substrates and that ubiquitylation of LPS triggers cell-autonomous immunity, and we postulate that non-proteinaceous substances other than LPS may also become ubiquitylated.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41586-021-03566-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:594:y:2021:i:7861:d:10.1038_s41586-021-03566-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-03566-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().