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

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.
Mesh Terms:
ADP Ribose Transferases, Adenosine Diphosphate Ribose, Animals, Binding Sites, Crystallography, X-Ray, Escherichia coli, HEK293 Cells, Histones, Humans, Isoenzymes, Kinetics, Mice, Molecular Docking Simulation, Molecular Dynamics Simulation, Mutation, Protein Binding, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Recombinant Proteins, Structure-Activity Relationship, Thermodynamics, ran GTP-Binding Protein
Date: Mar. 05, 2013
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