Imperial College London
Alternate

ProfessorDavidHolden

Faculty of Medicine, Department of Infectious Disease

Professor
 
 
 
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Contact

 

+44 (0)20 7594 3073d.holden

 
 
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Location

 

221Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Pruneda:2016:10.1016/j.molcel.2016.06.015,
author = {Pruneda, JN and Durkin, CH and Geurink, PP and Ovaa, H and Santhanam, B and Holden, DW and Komander, D},
doi = {10.1016/j.molcel.2016.06.015},
journal = {Molecular Cell},
pages = {261--276},
title = {The molecular basis for ubiquitin and ubiquitin-like specificities in bacterial effector proteases},
url = {http://dx.doi.org/10.1016/j.molcel.2016.06.015},
volume = {63},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Pathogenic bacteria rely on secreted effector proteins to manipulate host signaling pathways, often in creative ways. CE clan proteases, specific hydrolases for ubiquitin-like modifications (SUMO and NEDD8) in eukaryotes, reportedly serve as bacterial effector proteins with deSUMOylase, deubiquitinase, or, even, acetyltransferase activities. Here, we characterize bacterial CE protease activities, revealing K63-linkage-specific deubiquitinases in human pathogens, such as Salmonella, Escherichia, and Shigella, as well as ubiquitin/ubiquitin-like cross-reactive enzymes in Chlamydia, Rickettsia, and Xanthomonas. Five crystal structures, including ubiquitin/ubiquitin-like complexes, explain substrate specificities and redefine relationships across the CE clan. Importantly, this work identifies novel family members and provides key discoveries among previously reported effectors, such as the unexpected deubiquitinase activity in Xanthomonas XopD, contributed by an unstructured ubiquitin binding region. Furthermore, accessory domains regulate properties such as subcellular localization, as exemplified by a ubiquitin-binding domain in Salmonella Typhimurium SseL. Our work both highlights and explains the functional adaptations observed among diverse CE clan proteins.
AU  - Pruneda,JN
AU  - Durkin,CH
AU  - Geurink,PP
AU  - Ovaa,H
AU  - Santhanam,B
AU  - Holden,DW
AU  - Komander,D
DO  - 10.1016/j.molcel.2016.06.015
EP  - 276
PY  - 2016///
SN  - 1097-2765
SP  - 261
TI  - The molecular basis for ubiquitin and ubiquitin-like specificities in bacterial effector proteases
T2  - Molecular Cell
UR  - http://dx.doi.org/10.1016/j.molcel.2016.06.015
UR  - http://hdl.handle.net/10044/1/49613
VL  - 63
ER  -
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