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
- 1Department of Biological Structure,
- 2Biomolecular Structure and Design Program, University of Washington, Seattle, Washington 98195, USA;
- 3Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA;
- 4Department of Pharmacology,
- 5Department 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.
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Footnotes
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↵6 Corresponding author.
E-mail wxu{at}u.washington.edu.
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.182618.111.
- Received November 2, 2011.
- Accepted December 19, 2011.
- Copyright © 2012 by Cold Spring Harbor Laboratory Press
