Schubert, Alexander F., Nguyen, Justine, V, Franklin, Tyler G., Geurink, Paul P., Roberts, Cameron G., Sanderson, Daniel J., Miller, Lauren N., Ovaa, Huib, Hofmann, Kay ORCID: 0000-0002-2289-9083, Pruneda, Jonathan N. and Komander, David (2020). Identification and characterization of diverse OTU deubiquitinases in bacteria. Embo J., 39 (15). HOBOKEN: WILEY. ISSN 1460-2075

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Abstract

Manipulation of host ubiquitin signaling is becoming an increasingly apparent evolutionary strategy among bacterial and viral pathogens. By removing host ubiquitin signals, for example, invading pathogens can inactivate immune response pathways and evade detection. The ovarian tumor (OTU) family of deubiquitinases regulates diverse ubiquitin signals in humans. Viral pathogens have also extensively co-opted the OTU fold to subvert host signaling, but the extent to which bacteria utilize the OTU fold was unknown. We have predicted and validated a set of OTU deubiquitinases encoded by several classes of pathogenic bacteria. Biochemical assays highlight the ubiquitin and polyubiquitin linkage specificities of these bacterial deubiquitinases. By determining the ubiquitin-bound structures of two examples, we demonstrate the novel strategies that have evolved to both thread an OTU fold and recognize a ubiquitin substrate. With these new examples, we perform the first cross-kingdom structural analysis of the OTU fold that highlights commonalities among distantly related OTU deubiquitinases.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schubert, Alexander F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nguyen, Justine, VUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franklin, Tyler G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geurink, Paul P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roberts, Cameron G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanderson, Daniel J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miller, Lauren N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ovaa, HuibUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, KayUNSPECIFIEDorcid.org/0000-0002-2289-9083UNSPECIFIED
Pruneda, Jonathan N.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Komander, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-329408
DOI: 10.15252/embj.2020105127
Journal or Publication Title: Embo J.
Volume: 39
Number: 15
Date: 2020
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1460-2075
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
STRUCTURAL BASIS; MOLECULAR-BASIS; UBIQUITIN RECOGNITION; DOMAIN; SPECIFICITY; PROTEASES; ENZYMESMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/32940

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