Imperial College London
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ProfessorGadFrankel

Faculty of Natural Sciences, Department of Life Sciences

Professor of Molecular Pathogenesis
 
 
 
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Contact

 

+44 (0)20 7594 5253g.frankel

 
 
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Location

 

1.46Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Mylona:2019:10.26508/lsa.201800272,
author = {Mylona, E and Frankel, G},
doi = {10.26508/lsa.201800272},
journal = {Life Science Alliance},
title = {The S. Typhi effector StoD is an E3 ubiquitin ligase which binds K48- and K63-linked di-ubiquitin},
url = {http://dx.doi.org/10.26508/lsa.201800272},
volume = {2},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Salmonella enterica (e.g., 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 Å 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 β-sheet of ubiquitin, suggesting that StoD could simultaneously interact with two ubiquitin molecules. Consistently, StoD interacted with both K63- (KD = 5.6 ± 1 μM) and K48-linked diubiquitin (KD = 15 ± 4 μM). 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.
AU  - Mylona,E
AU  - Frankel,G
DO  - 10.26508/lsa.201800272
PY  - 2019///
SN  - 2575-1077
TI  - The S. Typhi effector StoD is an E3 ubiquitin ligase which binds K48- and K63-linked di-ubiquitin
T2  - Life Science Alliance
UR  - http://dx.doi.org/10.26508/lsa.201800272
UR  - http://hdl.handle.net/10044/1/70520
VL  - 2
ER  -
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