# Mechanism of atypical ubiquitination and deubiquitination by bacterial effectors

> **NIH NIH R01** · PURDUE UNIVERSITY · 2021 · $413,311

## Abstract

Project summary
Active modulation of host function is essential for the success of bacterial pathogens. The ubiquitin
network regulates virtually every cellular process in eukaryotes, particularly those involved in the
detection, recognition and response to infection. Accordingly, many pathogens target host ubiquitination
for their benefits. Earlier studies revealed that Legionella pneumophila, the causative agent of
Legionnaires' disease, interferes with host ubiquitin signaling by using at least 9 of its Dot/Icm effectors.
Our recent study revealed that members of the SidE effector family feature enzymatic domains with
unique activities for manipulating ubiquitin signals. First, these proteins contain a deubiquitinase (DUB)
module that efficiently removes ubiquitin from ubiquitinated proteins. Second, these proteins catalyze
ubiquitination by an unusual mechanism: the reaction does not require the E1, E2 enzymes or ATP,
factors that are essential for all described ubiquitination events. Furthermore, these novel ubiquitin
manipulating effectors are required for maximal intracellular bacterial replication, which differs sharply
with the majority of L. pneumophila Dot/Icm type IV effectors. As an additional layer of complexity, we
find that the biological activity of SidE effectors is regulated by the SidJ effector through its reversal of the
SidE-catalyzed ubiquitination by a mechanism that appears to distinctly differ from classical DUBs. By
biochemical and structural analyses, we will study the mechanism of action of these proteins. Different
functional domains encoded in these effectors seem to work in concert to regulate each other for a
balanced control of host functions. We will study biochemical basis of functional integration among
distinct activities present within these effectors. These studies will not only reveal novel mechanisms of
host function exploitation by intracellular pathogens, but also will have the potential to revise the current
understanding of ubiquitination, an enormously important signaling mechanism.

## Key facts

- **NIH application ID:** 10079495
- **Project number:** 5R01GM126296-04
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Chittaranjan Das
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $413,311
- **Award type:** 5
- **Project period:** 2018-01-16 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10079495

## Citation

> US National Institutes of Health, RePORTER application 10079495, Mechanism of atypical ubiquitination and deubiquitination by bacterial effectors (5R01GM126296-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10079495. Licensed CC0.

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