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A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation.

Publication ,  Journal Article
Pruneda, JN; Bastidas, RJ; Bertsoulaki, E; Swatek, KN; Santhanam, B; Clague, MJ; Valdivia, RH; Urbé, S; Komander, D
Published in: Nat Microbiol
December 2018

Pathogenic bacteria are armed with potent effector proteins that subvert host signalling processes during infection1. The activities of bacterial effectors and their associated roles within the host cell are often poorly understood, particularly for Chlamydia trachomatis2, a World Health Organization designated neglected disease pathogen. We identify and explain remarkable dual Lys63-deubiquitinase (DUB) and Lys-acetyltransferase activities in the Chlamydia effector ChlaDUB1. Crystal structures capturing intermediate stages of each reaction reveal how the same catalytic centre of ChlaDUB1 can facilitate such distinct processes, and enable the generation of mutations that uncouple the two activities. Targeted Chlamydia mutant strains allow us to link the DUB activity of ChlaDUB1 and the related, dedicated DUB ChlaDUB2 to fragmentation of the host Golgi apparatus, a key process in Chlamydia infection for which effectors have remained elusive. Our work illustrates the incredible versatility of bacterial effector proteins, and provides important insights towards understanding Chlamydia pathogenesis.

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Published In

Nat Microbiol

DOI

EISSN

2058-5276

Publication Date

December 2018

Volume

3

Issue

12

Start / End Page

1377 / 1384

Location

England

Related Subject Headings

  • Vero Cells
  • Protein Processing, Post-Translational
  • Protein Conformation
  • Mutation
  • Models, Molecular
  • Humans
  • Hela Cells
  • HeLa Cells
  • Golgi Apparatus
  • Gene Expression Regulation, Bacterial
 

Citation

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Pruneda, J. N., Bastidas, R. J., Bertsoulaki, E., Swatek, K. N., Santhanam, B., Clague, M. J., … Komander, D. (2018). A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation. Nat Microbiol, 3(12), 1377–1384. https://doi.org/10.1038/s41564-018-0271-y
Pruneda, Jonathan N., Robert J. Bastidas, Erithelgi Bertsoulaki, Kirby N. Swatek, Balaji Santhanam, Michael J. Clague, Raphael H. Valdivia, Sylvie Urbé, and David Komander. “A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation.Nat Microbiol 3, no. 12 (December 2018): 1377–84. https://doi.org/10.1038/s41564-018-0271-y.
Pruneda JN, Bastidas RJ, Bertsoulaki E, Swatek KN, Santhanam B, Clague MJ, et al. A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation. Nat Microbiol. 2018 Dec;3(12):1377–84.
Pruneda, Jonathan N., et al. “A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation.Nat Microbiol, vol. 3, no. 12, Dec. 2018, pp. 1377–84. Pubmed, doi:10.1038/s41564-018-0271-y.
Pruneda JN, Bastidas RJ, Bertsoulaki E, Swatek KN, Santhanam B, Clague MJ, Valdivia RH, Urbé S, Komander D. A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation. Nat Microbiol. 2018 Dec;3(12):1377–1384.

Published In

Nat Microbiol

DOI

EISSN

2058-5276

Publication Date

December 2018

Volume

3

Issue

12

Start / End Page

1377 / 1384

Location

England

Related Subject Headings

  • Vero Cells
  • Protein Processing, Post-Translational
  • Protein Conformation
  • Mutation
  • Models, Molecular
  • Humans
  • Hela Cells
  • HeLa Cells
  • Golgi Apparatus
  • Gene Expression Regulation, Bacterial