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Identification of a Class of Protein ADP-Ribosylating Sirtuins in Microbial Pathogens

DOI: 10.1016/j.molcel.2015.06.013 DOI Help
PMID: 26166706 PMID Help

Authors: Johannes Gregor Matthias Rack (University of Oxford) , Rosa Morra (University of Oxford) , Eva Barkauskaite (University of Oxford) , Rolf Kraehenbuehl (Cancer Research UK Manchester Institute) , Antonio Ariza (University of Oxford) , Yue Qu (Monash University) , Mary Ortmayer (University of Manchester) , Orsolya Leidecker (Max Planck Institute for Biology of Ageing) , David r Cameron (The Alfred Hospital and Monash University) , Ivan Matic (Max Planck Institute for Biology of Ageing) , Anton y. Peleg (Monash University) , David Leys (School of Chemistry & Manchester Interdisciplinary Biocentre, The University of Manchester) , Ana Traven (Monash University) , Ivan Ahel (Monash University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Molecular Cell , VOL 59 (2) , PAGES 309–320

State: Published (Approved)
Published: July 2015
Diamond Proposal Number(s): 9306

Open Access Open Access

Abstract: 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.

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

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