Structure-function analyses reveal the mechanism of the ARH3-dependent hydrolysis of ADP-ribosylation.

ABSTRACT: ADP-ribosylation of proteins plays key roles in multiple biological processes, including DNA damage repair. Recent evidence suggests that serine is an important acceptor for ADP-ribosylation, and that serine ADP-ribosylation is hydrolyzed by ADP-ribosylhydrolase 3 (ARH3 or ADPRHL2). However, the structural details in ARH3-mediated hydrolysis remain elusive. Here, we determined the structure of ARH3 in a complex with ADP-ribose (ADPR). Our analyses revealed a group of acidic residues in ARH3 that keep two Mg²⁺ ions at the catalytic center for hydrolysis of Ser-linked ADP-ribosyl group. In particular, dynamic conformational changes involving Glu⁴¹ were observed in the catalytic center. Our observations suggest that Mg²⁺ ions together with Glu⁴¹ and

SUBMITTER: Wang M 

PROVIDER: S-EPMC6139573 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature