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UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids

Author

Listed:
  • Dawn M. Wenzel

    (Box 357350, University of Washington)

  • Alexei Lissounov

    (Box 357350, University of Washington)

  • Peter S. Brzovic

    (Box 357350, University of Washington)

  • Rachel E. Klevit

    (Box 357350, University of Washington)

Abstract

E2/E3-mediated ubiquitination Attachment of the small protein ubiquitin (Ub) to substrates is a reversible covalent modification that regulates the stability, activity and localization of target proteins. Assembly of ubiquitin chains requires three enzyme activities: a Ub-activating (E1) enzyme, a Ub-conjugating (E2) enzyme and a Ub ligase (E3). E2 enzymes are responsible both for E3 selection and substrate modification and for much of the diversity of Ub cellular signalling. The E2 UbcH7 shows broad specificity for HECT-type E3, but often fails to function with RING E3s despite its ability to form specific complexes. Rachel Klevit and colleagues demonstrate that UbcH7 exhibits robust activity with a family of E3 ligases that are RING/HECT hybrids: they bind to E2s through a RING domain but transfer Ub through a HECT-like mechanism. They propose that the intrinsic chemical reactivity of an E2 is a powerful predictor in determining with which class of E3 it will function.

Suggested Citation

  • Dawn M. Wenzel & Alexei Lissounov & Peter S. Brzovic & Rachel E. Klevit, 2011. "UBCH7 reactivity profile reveals parkin and HHARI to be RING/HECT hybrids," Nature, Nature, vol. 474(7349), pages 105-108, June.
  • Handle: RePEc:nat:nature:v:474:y:2011:i:7349:d:10.1038_nature09966
    DOI: 10.1038/nature09966
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    Cited by:

    1. Xiangyi S. Wang & Thomas R. Cotton & Sarah J. Trevelyan & Lachlan W. Richardson & Wei Ting Lee & John Silke & Bernhard C. Lechtenberg, 2023. "The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Véronique Sauvé & Eric Stefan & Nathalie Croteau & Thomas Goiran & Rayan Fakih & Nupur Bansal & Adelajda Hadzipasic & Jing Fang & Paramasivam Murugan & Shimin Chen & Edward A. Fon & Warren D. Hirst & , 2024. "Activation of parkin by a molecular glue," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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