Structural highlights
Function
[CDUB1_CHLT2] Effector proteins function to alter host cell physiology and promote bacterial survival in host tissues. This protease possesses deubiquitinating and deneddylating activities (By similarity). Impairs ubiquitination and degradation of NF-kappa-B inhibitor alpha (NFKBIA), thereby preventing NF-kappa-B activation.[1]
Publication Abstract from PubMed
Pathogenic bacteria are armed with potent effector proteins that subvert host signalling processes during infection(1). The activities of bacterial effectors and their associated roles within the host cell are often poorly understood, particularly for Chlamydia trachomatis(2), 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.
A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation.,Pruneda JN, Bastidas RJ, Bertsoulaki E, Swatek KN, Santhanam B, Clague MJ, Valdivia RH, Urbe S, Komander D Nat Microbiol. 2018 Nov 5. pii: 10.1038/s41564-018-0271-y. doi:, 10.1038/s41564-018-0271-y. PMID:30397340[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Le Negrate G, Krieg A, Faustin B, Loeffler M, Godzik A, Krajewski S, Reed JC. ChlaDub1 of Chlamydia trachomatis suppresses NF-kappaB activation and inhibits IkappaBalpha ubiquitination and degradation. Cell Microbiol. 2008 Sep;10(9):1879-92. doi: 10.1111/j.1462-5822.2008.01178.x., Epub 2008 Jun 28. PMID:18503636 doi:http://dx.doi.org/10.1111/j.1462-5822.2008.01178.x
- ↑ Pruneda JN, Bastidas RJ, Bertsoulaki E, Swatek KN, Santhanam B, Clague MJ, Valdivia RH, Urbe S, Komander D. A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation. Nat Microbiol. 2018 Nov 5. pii: 10.1038/s41564-018-0271-y. doi:, 10.1038/s41564-018-0271-y. PMID:30397340 doi:http://dx.doi.org/10.1038/s41564-018-0271-y
