The molecular basis for ubiquitin and ubiquitin-like specificities in bacterial effector proteases
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2016-07-14
Date Acceptance
2016-06-08
Citation
Molecular Cell, 2016, 63 (2), pp.261-276
ISSN
1097-2765
Publisher
Elsevier (Cell Press)
Start Page
261
End Page
276
Journal / Book Title
Molecular Cell
Volume
63
Issue
2
Copyright Statement
© 2016 The Authors. Published by Elsevier Inc.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Medical Research Council (MRC)
Grant Number
MR/K027077/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
SUBSTRATE-SPECIFICITY
STRUCTURAL BASIS
ADENOVIRUS PROTEINASE
SALMONELLA
YOPJ
DEUBIQUITINASE
YERSINIA
ACTIVATION
BINDING
POLYUBIQUITIN
Publication Status
Published