A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation

Jonathan Pruneda, Robert J. Bastidas, Erithelgi Bertsoulaki, Kirby N. Swatek, Balaji Santhanam, Michael J. Clague, Raphael H. Valdivia, Sylvie Urbé, David Komander

Research output: Contribution to journalLetter

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1377-1384
Number of pages8
JournalNature Microbiology
Volume3
Issue number12
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

Fingerprint

Chlamydia
Acetylation
Neglected Diseases
Chlamydia Infections
Acetyltransferases
Bacterial Proteins
Golgi Apparatus
Bacteria
Mutation
Deubiquitinating Enzymes
Proteins

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

Cite this

Pruneda, J., 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. Nature Microbiology, 3(12), 1377-1384. https://doi.org/10.1038/s41564-018-0271-y

A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation. / Pruneda, Jonathan; Bastidas, Robert J.; Bertsoulaki, Erithelgi; Swatek, Kirby N.; Santhanam, Balaji; Clague, Michael J.; Valdivia, Raphael H.; Urbé, Sylvie; Komander, David.

In: Nature Microbiology, Vol. 3, No. 12, 01.12.2018, p. 1377-1384.

Research output: Contribution to journalLetter

Pruneda, J, Bastidas, RJ, Bertsoulaki, E, Swatek, KN, Santhanam, B, Clague, MJ, Valdivia, RH, Urbé, S & Komander, D 2018, 'A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation', Nature Microbiology, vol. 3, no. 12, pp. 1377-1384. https://doi.org/10.1038/s41564-018-0271-y
Pruneda, Jonathan ; Bastidas, Robert J. ; Bertsoulaki, Erithelgi ; Swatek, Kirby N. ; Santhanam, Balaji ; Clague, Michael J. ; Valdivia, Raphael H. ; Urbé, Sylvie ; Komander, David. / A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation. In: Nature Microbiology. 2018 ; Vol. 3, No. 12. pp. 1377-1384.
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