Bacterial otu deubiquitinases regulate substrate ubiquitination upon legionella infection

Donghyuk Shin, Anshu Bhattacharya, Yi Lin Cheng, Marta Campos Alonso, Ahmad Reza Mehdipour, Gerbrand J. van der Heden van Noort, Huib Ovaa, Gerhard Hummer, Ivan Dikic

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

Abstract

Legionella pneumophila causes a severe pneumonia known as Legionnaires’ disease. During the infection, Legionella injects more than 300 effector proteins into host cells. Among them are enzymes involved in altering the host-ubiquitination system. Here, we identified two LegionellaOTU (ovarian tumor)-like deubiquitinases (LOT-DUBs; LotB [Lpg1621/Ceg23] and LotC [Lpg2529]). The crystal structure of the LotC catalytic core (LotC14-310 ) was determined at 2.4 Å. Unlike the classical OTU-family, the LOT-family shows an extended helical lobe between the Cys-loop and the variable loop, which defines them as a unique class of OTU-DUBs. LotB has an additional ubiquitin-binding site (S1’), which enables the specific cleavage of Lys63-linked polyubiquitin chains. By contrast, LotC only contains the S1 site and cleaves different species of ubiquitin chains. MS analysis of LotB and LotC identified different categories of host-interacting proteins and substrates. Together, our results provide new structural insights into bacterial OTU-DUBs and indicate distinct roles in host–pathogen interactions.

Original languageEnglish
Article numbere58277
Pages (from-to)1-21
Number of pages21
JournaleLife
Volume9
DOIs
Publication statusPublished - 2020 Oct

Bibliographical note

Publisher Copyright:
© Shin et al.

All Science Journal Classification (ASJC) codes

  • General Neuroscience
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

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