Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains - PubMed (original) (raw)

. 2013 Mar 5;21(3):462-75.

doi: 10.1016/j.str.2012.12.019.

Tobias Karlberg, Nicolas Herzog, Ann-Gerd Thorsell, Annika Gross, Karla L H Feijs, Patricia Verheugd, Petri Kursula, Bianca Nijmeijer, Elisabeth Kremmer, Henning Kleine, Andreas G Ladurner, Herwig Schüler, Bernhard Lüscher

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Recognition of mono-ADP-ribosylated ARTD10 substrates by ARTD8 macrodomains

Alexandra H Forst et al. Structure. 2013.

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Abstract

ADP-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.

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