A Clickable Aminooxy Probe for Monitoring Cellular ADP-Ribosylation

Rory K. Morgan, Michael S. Cohen

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

ADP-ribosylation is essential for cell function, yet there is a dearth of methods for detecting this post-translational modification in cells. Here, we describe a clickable aminooxy alkyne (AO-alkyne) probe that can detect cellular ADP-ribosylation on acidic amino acids following Cu-catalyzed conjugation to an azide-containing reporter. Using AO-alkyne, we show that PARP10 and PARP11 are auto-ADP-ribosylated in cells. We also demonstrate that AO-alkyne can be used to monitor stimulus-induced ADP-ribosylation in cells. Functional studies using AO-alkyne support a previously unknown mechanism for ADP-ribosylation on acidic amino acids, wherein a glutamate or aspartate at the initial C1′-position of ADP-ribose transfers to the C2′ position. This new mechanism for ADP-ribosylation has important implications for how glutamyl/aspartyl-ADP-ribose is recognized by proteins in cells.

Original languageEnglish (US)
Pages (from-to)1778-1784
Number of pages7
JournalACS chemical biology
Volume10
Issue number8
DOIs
StatePublished - Aug 21 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

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