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

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Dangosydd eitem ddigidol (DOI)

  • Johannes Gregor Matthias Rack
    University Department of Psychiatry, Warneford Hospital, Oxford
  • Rosa Morra
    Manchester University
  • Eva Barkauskaite
    University Department of Psychiatry, Warneford Hospital, Oxford
  • Rolf Kraehenbuehl
    Cancer Research UK Manchester Institute
  • Antonio Ariza
    University Department of Psychiatry, Warneford Hospital, Oxford
  • Yue Qu
    Monash University
  • Mary Ortmayer
    Manchester University
  • 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
    Manchester University
  • Ana Traven
    Monash University
  • Ivan Ahel
    University Department of Psychiatry, Warneford Hospital, Oxford

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.

Allweddeiriau

Iaith wreiddiolSaesneg
Tudalennau (o-i)309-20
Nifer y tudalennau12
CyfnodolynMolecular Cell
Cyfrol59
Rhif y cyfnodolyn2
Dyddiad ar-lein cynnar9 Gorff 2015
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 16 Gorff 2015
Cyhoeddwyd yn allanolIe
Gweld graff cysylltiadau