| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2029798 | Structure | 2013 | 14 Pages |
SummaryADP-ribosyltransferases (ARTs) catalyze the transfer of ADP-ribose from NAD+ onto substrates. Some ARTs generate in an iterative process ADP-ribose polymers that serve as adaptors for distinct protein domains. Other ARTs, exemplified by ARTD10, function as mono-ADP-ribosyltransferases, but it has been unclear whether this modification occurs in cells and how it is read. We observed that ARTD10 colocalized with ARTD8 and defined its macrodomains 2 and 3 as readers of mono-ADP-ribosylation both in vitro and in cells. The crystal structures of these two ARTD8 macrodomains and isothermal titration calorimetry confirmed their interaction with ADP-ribose. These macrodomains recognized mono-ADP-ribosylated ARTD10, but not poly-ADP-ribosylated ARTD1. This distinguished them from the macrodomain of macroH2A1.1, which interacted with poly- but not mono-ADP-ribosylated substrates. Moreover, Ran, an ARTD10 substrate, was also read by ARTD8 macrodomains. This identifies readers of mono-ADP-ribosylated proteins, defines their structures, and demonstrates the presence of this modification in cells.
Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (215 K)Download as PowerPoint slideHighlights► ARTD8 macrodomains read ARTD10-dependent mono-ADP-ribosylation ► The structure of ARTD8 macrodomains reveals a conserved fold for ADP-ribose binding ► Distinct macrodomains read mono- and poly-ADP-ribosylation selectively ► ARTD8 macrodomains can be used to visualize mono-ADP-ribosylation in cells
