Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens
Research output: Contribution to journal › Article › peer-review
Electronic versions
DOI
Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity. In our model organisms, Staphylococcus aureus and Streptococcus pyogenes, the activity is dependent on prior lipoylation of the target protein and can be reversed by a sirtuin-associated macrodomain protein. Together, our data describe a sirtuin-dependent reversible protein ADP-ribosylation system and establish a crosstalk between lipoylation and mono-ADP-ribosylation. We propose that these posttranslational modifications modulate microbial virulence by regulating the response to host-derived reactive oxygen species.
Keywords
- Adenosine Diphosphate Ribose/metabolism, Bacterial Proteins/chemistry, Catalytic Domain, Crystallography, X-Ray, Genes, Bacterial, HEK293 Cells, Host-Pathogen Interactions, Humans, Lactobacillales/enzymology, Lipoylation, Models, Molecular, Operon, Oxidative Stress, Phylogeny, Protein Conformation, Sirtuins/chemistry, Staphylococcus aureus/enzymology, Streptococcus pyogenes/enzymology
Original language | English |
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Pages (from-to) | 309-20 |
Number of pages | 12 |
Journal | Molecular Cell |
Volume | 59 |
Issue number | 2 |
Early online date | 9 Jul 2015 |
DOIs | |
Publication status | Published - 16 Jul 2015 |
Externally published | Yes |