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Genes & Dev. 26 (3): 235-240

Copyright © 2012 by Cold Spring Harbor Laboratory Press.

RESEARCH COMMUNICATION

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

Zhizhi Wang1,2, Gregory A. Michaud3, Zhihong Cheng1, Yue Zhang3, Thomas R. Hinds4, Erkang Fan1,5, Feng Cong3,, and Wenqing Xu1,6

1 Department of Biological Structure,
2 Biomolecular Structure and Design Program, University of Washington, Seattle, Washington 98195, USA;
3 Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA;
4 Department of Pharmacology,
5 Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA

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.

Key Words: poly(ADP-ribosyl)ation • ubiquitination • WWE domain • PARP-1 • axin • crystal structure

Received for publication November 2, 2011. Accepted for publication December 19, 2011.

6 Corresponding author.

E-mail wxu{at}u.washington.edu.

Supplemental material is available for this article.

Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.182618.111.

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