A chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation



Pruneda, Jonathan, Robert, Bastidas, Bertsoulaki, Erithelgi, Swatek, Kirby, Santhanam, Balaji, Clague, MJ ORCID: 0000-0003-3355-9479, Valdivia, Raphael, Urbe, Sylvie ORCID: 0000-0003-4735-9814 and Komander, David
(2018) A chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation. Nature Microbiology, 3 (12). pp. 1377-1384.

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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.

Item Type: Article
Uncontrolled Keywords: Bacterial pathogenesis, Pathogens, Ubiquitylation, X-ray crystallography
Depositing User: Symplectic Admin
Date Deposited: 07 Nov 2018 08:54
Last Modified: 19 Jan 2023 01:13
DOI: 10.1038/s41564-018-0271-y
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3028489