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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 261-276 |
| Number of pages | 16 |
| Journal | Molecular Cell |
| Volume | 63 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 21 2016 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
The Molecular Basis for Ubiquitin and Ubiquitin-like Specificities in Bacterial Effector Proteases. / Pruneda, Jonathan; Durkin, Charlotte H.; Geurink, Paul P.; Ovaa, Huib; Santhanam, Balaji; Holden, David W.; Komander, David.
In: Molecular Cell, Vol. 63, No. 2, 21.07.2016, p. 261-276.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Molecular Basis for Ubiquitin and Ubiquitin-like Specificities in Bacterial Effector Proteases
AU - Pruneda, Jonathan
AU - Durkin, Charlotte H.
AU - Geurink, Paul P.
AU - Ovaa, Huib
AU - Santhanam, Balaji
AU - Holden, David W.
AU - Komander, David
PY - 2016/7/21
Y1 - 2016/7/21
N2 - 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.
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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84978880194&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2016.06.015
DO - 10.1016/j.molcel.2016.06.015
M3 - Article
C2 - 27425412
AN - SCOPUS:84978880194
VL - 63
SP - 261
EP - 276
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 2
ER -