TY - JOUR
T1 - A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation
AU - Pruneda, Jonathan N.
AU - Bastidas, Robert J.
AU - Bertsoulaki, Erithelgi
AU - Swatek, Kirby N.
AU - Santhanam, Balaji
AU - Clague, Michael J.
AU - Valdivia, Raphael H.
AU - Urbé, Sylvie
AU - Komander, David
N1 - Publisher Copyright:
© 2018, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85055991245&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055991245&partnerID=8YFLogxK
U2 - 10.1038/s41564-018-0271-y
DO - 10.1038/s41564-018-0271-y
M3 - Letter
C2 - 30397340
AN - SCOPUS:85055991245
SN - 2058-5276
VL - 3
SP - 1377
EP - 1384
JO - Nature Microbiology
JF - Nature Microbiology
IS - 12
ER -