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 (original) (raw)

  1. Gregory A. Michaud3,
  2. Zhihong Cheng1,
  3. Yue Zhang3,
  4. Thomas R. Hinds4,
  5. Erkang Fan1,5,
  6. Feng Cong3 and
  7. Wenqing Xu1,6
  8. 1Department of Biological Structure,
  9. 2Biomolecular Structure and Design Program, University of Washington, Seattle, Washington 98195, USA;
  10. 3Novartis Institutes for Biomedical Research, Cambridge, Massachusetts 02139, USA;
  11. 4Department of Pharmacology,
  12. 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.

Footnotes