Chlamydia trachomatis-containing vacuole serves as deubiquitination platform to stabilize Mcl-1 and to interfere with host defense
Please always quote using this URN: urn:nbn:de:bvb:20-opus-171073
- Obligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of this domain revealed high similarity to mammalian deubiquitinases with a unique α-helix close to the substrate-binding pocket. We identified the apoptosis regulator Mcl-1 as a target that interacts withObligate intracellular Chlamydia trachomatis replicate in a membrane-bound vacuole called inclusion, which serves as a signaling interface with the host cell. Here, we show that the chlamydial deubiquitinating enzyme (Cdu) 1 localizes in the inclusion membrane and faces the cytosol with the active deubiquitinating enzyme domain. The structure of this domain revealed high similarity to mammalian deubiquitinases with a unique α-helix close to the substrate-binding pocket. We identified the apoptosis regulator Mcl-1 as a target that interacts with Cdu1 and is stabilized by deubiquitination at the chlamydial inclusion. A chlamydial transposon insertion mutant in the Cdu1-encoding gene exhibited increased Mcl-1 and inclusion ubiquitination and reduced Mcl-1 stabilization. Additionally, inactivation of Cdu1 led to increased sensitivity of C. trachomatis for IFNγ and impaired infection in mice. Thus, the chlamydial inclusion serves as an enriched site for a deubiquitinating activity exerting a function in selective stabilization of host proteins and protection from host defense.…
Author: | Annette FischerORCiD, Kelly S Harrison, Yesid Ramirez, Daniela Auer, Suvagata Roy Chowdhury, Bhupesh K PrustyORCiD, Florian Sauer, Zoe Dimond, Caroline Kisker, P Scott Hefty, Thomas RudelORCiD |
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URN: | urn:nbn:de:bvb:20-opus-171073 |
Document Type: | Journal article |
Faculties: | Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften |
Fakultät für Biologie / Rudolf-Virchow-Zentrum | |
Language: | English |
Parent Title (English): | eLife |
Year of Completion: | 2017 |
Volume: | 6 |
Issue: | e21465 |
Source: | eLife 2017, 6:e21465. DOI: 10.7554/eLife.21465.001 |
DOI: | https://doi.org/10.7554/eLife.21465 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Tag: | Chlamydia trachomatis; Mcl-1; cell-autonomous defense; deubiquitinase |
Release Date: | 2019/10/15 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |