Journal
LIFE SCIENCE ALLIANCE
Volume 2, Issue 3, Pages -Publisher
LIFE SCIENCE ALLIANCE LLC
DOI: 10.26508/lsa.201800272
Keywords
-
Categories
Funding
- Wellcome Trust [100298/Z/12/Z]
- Wellcome Trust Investigator Award [107057/Z/15/Z]
- BBSRC [BB/K001515/1]
- MRC
- BBSRC
- Wellcome Trust [100298/Z/12/Z, 107057/Z/15/Z] Funding Source: Wellcome Trust
- BBSRC [BB/K001515/1] Funding Source: UKRI
- MRC [MR/M011984/1, MR/P028225/1, MR/S021264/1] Funding Source: UKRI
Ask authors/readers for more resources
Salmonella enterica (eg., serovars Typhi and Typhimurium) relies on translocation of effectors via type III secretion systems (T3SS). Specialization of typhoidal serovars is thought to be mediated via pseudogenesis. Here, we show that the Salmonella Typhi STY1076/t1865 protein, named StoD, a homologue of the enteropathogenic Escherichia coli/enterohemorrhagic E. coli/Citrobacter rodentium NleG, is a T3SS effector. The StoD C terminus (StoD-C) is a U-box E3 ubiquitin ligase, capable of autoubiquitination in the presence of multiple E2s. The crystal structure of the StoD N terminus (StoD-N) at 2.5 angstrom resolution revealed a ubiquitin-like fold. In HeLa cells expressing StoD, ubiquitin is redistributed into puncta that colocalize with StoD. Binding assays showed that StoD-N and StoD-C bind the same exposed surface of the beta-sheet of ubiquitin, suggesting that StoD could simultaneously interact with two ubiquitin molecules. Consistently, StoD interacted with both K63- (K-D = 5.6 +/- 1 mu M) and K48-linked diubiquitin (K-D = 15 +/- 4 mu m). Accordingly, we report the first S. Typhi-specific T3SS effector. We suggest that StoD recognizes and ubiquitinates pre-ubiquitinated targets, thus subverting intracellular signaling by functioning as an E4 enzyme.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available