E2 conjugating enzymes must disengage from their E1 enzymes before E3-dependent ubiquitin and ubiquitin-like transfer (original) (raw)

Nature Structural & Molecular Biology volume 12, pages 933–934 (2005)Cite this article

Abstract

During ubiquitin ligation, an E2 conjugating enzyme receives ubiquitin from an E1 enzyme and then interacts with an E3 ligase to modify substrates. Competitive binding experiments with three human E2-E3 protein pairs show that the binding of E1s and of E3s to E2s are mutually exclusive. These results imply that polyubiquitination requires recycling of E2 for addition of successive ubiquitins to substrate.

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$209.00 per year

only $17.42 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

Similar content being viewed by others

Accession codes

Accessions

BINDPlus

References

  1. Huang, L. et al. Science 286, 1321–1326 (1999).
    Article CAS Google Scholar
  2. Zheng, N., Wang, P., Jeffrey, P.D. & Pavletich, N.P. Cell 102, 533–539 (2000).
    Article CAS Google Scholar
  3. Huang, D.T. et al. Mol. Cell 17, 341–350 (2005).
    Article CAS Google Scholar
  4. Kuhlman, B. et al. Science 302, 1364–1368 (2003).
    Article CAS Google Scholar
  5. Pickart, C.M. & Eddins, M.J. Biochim. Biophys. Acta 1695, 55–72 (2004).
    Article CAS Google Scholar
  6. Hamilton, K.S. et al. Structure (Camb.) 9, 897–904 (2001).
    Article CAS Google Scholar
  7. Siepmann, T.J., Bohnsack, R.N., Tokgoz, Z., Baboshina, O.V. & Haas, A.L. J. Biol. Chem. 278, 9448–9457 (2003).
    Article CAS Google Scholar
  8. Kawakami, T. et al. EMBO J. 20, 4003–4012 (2001).
    Article CAS Google Scholar
  9. Carroll, C.W. & Morgan, D.O. Nat. Cell Biol. 4, 880–887 (2002).
    Article CAS Google Scholar
  10. Deffenbaugh, A.E. et al. Cell 114, 611–622 (2003).
    Article CAS Google Scholar

Download references

Acknowledgements

We thank P. Howley and J. Huibregtse for clones of the E6AP-HECT domain and UbcH7. B.K. acknowledges funding from the US National Institutes of Health (NIH), the Searle Scholar's Program and the Beckman Foundation. B.A.S. acknowledges funding from American Lebanese Syrian Associated Charities (ALSAC), the NIH (P30CA21765, R01GM69530), the Philip and Elizabeth Gross Foundation, the Beckman Foundation and the Pew Scholar's Program. D.M.D. acknowledges support from the American Cancer Society.

Author information

Author notes

  1. Ziad M Eletr and Danny T Huang: These authors contributed equally to the work.

Authors and Affiliations

  1. Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, 27599-7260, North Carolina, USA
    Ziad M Eletr & Brian Kuhlman
  2. Department of Structural Biology and Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, 38105, Tennessee, USA
    Danny T Huang, David M Duda & Brenda A Schulman

Authors

  1. Ziad M Eletr
    You can also search for this author inPubMed Google Scholar
  2. Danny T Huang
    You can also search for this author inPubMed Google Scholar
  3. David M Duda
    You can also search for this author inPubMed Google Scholar
  4. Brenda A Schulman
    You can also search for this author inPubMed Google Scholar
  5. Brian Kuhlman
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toBrian Kuhlman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

About this article

Cite this article

Eletr, Z., Huang, D., Duda, D. et al. E2 conjugating enzymes must disengage from their E1 enzymes before E3-dependent ubiquitin and ubiquitin-like transfer.Nat Struct Mol Biol 12, 933–934 (2005). https://doi.org/10.1038/nsmb984

Download citation

This article is cited by