@article{f60ebf014ee84f2a87bc35b1ab0c870d,
title = "Identification and characterization of diverse OTU deubiquitinases in bacteria",
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.",
keywords = "bacterial effector, deubiquitinase, pathogen, protein structure, ubiquitin",
author = "Schubert, {Alexander F.} and Nguyen, {Justine V.} and Franklin, {Tyler G.} and Geurink, {Paul P.} and Roberts, {Cameron G.} and Sanderson, {Daniel J.} and Miller, {Lauren N.} and Huib Ovaa and Kay Hofmann and Pruneda, {Jonathan N.} and David Komander",
note = "Funding Information: We would like to thank the beamline staff at DLS I04, I04-1, and I24 for their assistance. Access to DLS was supported, in part, by the EU FP7 infrastructure grant BIOSTRUCT-X (contract no. 283570). This work was supported by a VICI grant from the Netherlands Organization for Scientific Research N.W.O. (724.013.002, HO), the Medical Research Council (U105192732, DK), the European Research Council (309756 and 724804, DK), the Lister Institute for Preventative Medicine (DK), an EMBO Long-Term Fellowship (JNP), Oregon Health & Science University (JNP), and The Collins Medical Trust in Portland, OR (JNP). TGF was supported by 5T32GM071338-14, Program in Molecular and Cellular Biosciences. Funding Information: We would like to thank the beamline staff at DLS I04, I04‐1, and I24 for their assistance. Access to DLS was supported, in part, by the EU FP7 infrastructure grant BIOSTRUCT‐X (contract no. 283570). This work was supported by a VICI grant from the Netherlands Organization for Scientific Research N.W.O. (724.013.002, HO), the Medical Research Council (U105192732, DK), the European Research Council (309756 and 724804, DK), the Lister Institute for Preventative Medicine (DK), an EMBO Long‐Term Fellowship (JNP), Oregon Health & Science University (JNP), and The Collins Medical Trust in Portland, OR (JNP). TGF was supported by 5T32GM071338‐14, Program in Molecular and Cellular Biosciences. Publisher Copyright: {\textcopyright} 2020 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2020",
month = aug,
day = "3",
doi = "10.15252/embj.2020105127",
language = "English (US)",
volume = "39",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "15",
}