Mechanistic insights into the three steps of poly(ADP-ribosylation) reversal

نویسندگان

چکیده

Abstract Poly(ADP-ribosyl)ation (PAR) is a versatile and complex posttranslational modification composed of repeating units ADP-ribose arranged into linear or branched polymers. This scaffold linked to the regulation many cellular processes including DNA damage response, alteration chromatin structure Wnt signalling. Despite decades research, principles mechanisms underlying all steps PAR removal remain actively studied. In this work, we synthesise well-defined branch point molecules demonstrate that PARG, but not ARH3, can resolve distinct architecture. Structural analysis ARH3 in with dimeric as well an ADP-ribosylated peptide reveal molecular basis for hydrolysis terminal linkages. We find ARH3-dependent requires both rearrangement catalytic glutamate induction unusual, square-pyramidal magnesium coordination geometry.

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ژورنال

عنوان ژورنال: Nature Communications

سال: 2021

ISSN: ['2041-1723']

DOI: https://doi.org/10.1038/s41467-021-24723-3