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

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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