• search hit 3 of 814
Back to Result List

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.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
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
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):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International