Recognition of the Iso-ADP-ribose Moiety in Poly(ADP-ribose) by WWE Domains Suggests a General Mechanism for Poly(ADP-ribosyl)ation-dependent Ubiquitination

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2012 Jan 24

PMID 22267412

Citations 146

Authors

Zhizhi Wang

Gregory A Michaud

Zhihong Cheng

Yue Zhang

Thomas R Hinds

Erkang Fan

Feng Cong

Wenqing Xu

Affiliations

Soon will be listed here.

Abstract

Protein poly(ADP-ribosyl)ation and ubiquitination are two key post-translational modifications regulating many biological processes. Through crystallographic and biochemical analysis, we show that the RNF146 WWE domain recognizes poly(ADP-ribose) (PAR) by interacting with iso-ADP-ribose (iso-ADPR), the smallest internal PAR structural unit containing the characteristic ribose-ribose glycosidic bond formed during poly(ADP-ribosyl)ation. The key iso-ADPR-binding residues we identified are highly conserved among WWE domains. Binding assays further demonstrate that PAR binding is a common function for the WWE domain family. Since many WWE domain-containing proteins are known E3 ubiquitin ligases, our results suggest that protein poly(ADP-ribosyl)ation may be a general mechanism to target proteins for ubiquitination.

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