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A RING E3–substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases

Abstract

How RING E3 ligases mediate E2-to-substrate ubiquitin-like protein (UBL) transfer remains unknown. Here we address how the RING E3 RBX1 positions NEDD8's E2 (UBC12) and substrate (CUL1). We find that existing structures are incompatible with CUL1 NEDD8ylation and report a new conformation of RBX1 that places UBC12 adjacent to CUL1. We propose RING domain rotation as a general mechanism for UBL transfer for the largest family of E3s.

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Figure 1: UBC12–RBX1 interactions.
Figure 2: Models from prior structures reveal an E2-to-substrate gap.
Figure 3: Structure of CUL1CTD–RBX1 in new conformation.

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References

  1. Deshaies, R.J. & Joazeiro, C.A. Annu. Rev. Biochem. 78, 399–434 (2009).

    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. Mace, P.D. et al. J. Biol. Chem. 283, 31633–31640 (2008).

    Article  CAS  Google Scholar 

  4. Yin, Q. et al. Nat. Struct. Mol. Biol. 16, 658–666 (2009).

    Article  CAS  Google Scholar 

  5. Zimmerman, E.S., Schulman, B.A. & Zheng, N. Curr. Opin. Struct. Biol. 20, 714–721 (2010).

    Article  CAS  Google Scholar 

  6. Duda, D.M. et al. Curr. Opin. Struct. Biol. 21, 257–264 (2011).

    Article  CAS  Google Scholar 

  7. Zheng, N. et al. Nature 416, 703–709 (2002).

    Article  CAS  Google Scholar 

  8. Goldenberg, S.J. et al. Cell 119, 517–528 (2004).

    Article  CAS  Google Scholar 

  9. Kamura, T., Conrad, M.N., Yan, Q., Conaway, R.C. & Conaway, J.W. Genes Dev. 13, 2928–2933 (1999).

    Article  CAS  Google Scholar 

  10. Kurz, T. et al. Mol. Cell 29, 23–35 (2008).

    Article  CAS  Google Scholar 

  11. Kim, A.Y. et al. J. Biol. Chem. 283, 33211–33220 (2008).

    Article  CAS  Google Scholar 

  12. Scott, D.C. et al. Mol. Cell 39, 784–796 (2010).

    Article  CAS  Google Scholar 

  13. Duda, D.M. et al. Cell 134, 995–1006 (2008).

    Article  CAS  Google Scholar 

  14. Yamoah, K. et al. Proc. Natl. Acad. Sci. USA 105, 12230–12235 (2008).

    Article  CAS  Google Scholar 

  15. Saha, A. & Deshaies, R.J. Mol. Cell 32, 21–31 (2008).

    Article  CAS  Google Scholar 

  16. Wu, K., Kovacev, J. & Pan, Z.Q. Mol. Cell 37, 784–796 (2010).

    Article  CAS  Google Scholar 

  17. Pierce, N.W., Kleiger, G., Shan, S.O. & Deshaies, R.J. Nature 462, 615–619 (2009).

    Article  CAS  Google Scholar 

  18. Soucy, T.A. et al. Nature 458, 732–736 (2009).

    Article  CAS  Google Scholar 

  19. Angers, S. et al. Nature 443, 590–593 (2006).

    Article  CAS  Google Scholar 

  20. Huang, D.T. et al. Mol. Cell 33, 483–495 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by American Lebanese Syrian Associated Charities (ALSAC), the St. Jude Cancer Center Core grant, US National Institutes of Health (NIH) grants R01GM069530 to B.A.S. and R01CA082491 to R.W.K. and the Howard Hughes Medical Institute (HHMI). B.A.S. is an Investigator of the HHMI, and M.F.C. is an HHMI postdoctoral fellow of the Damon Runyon Cancer Research Foundation (DRG 2021-9). We thank A. Nourse for analytical ultracentrifugation experiments, J. Monda for experimental assistance and discussions, and D.W. Miller, S. Bozeman, D.J. Miller and J. Bollinger for administrative and computational support. NE-CAT is supported by NIH grant NCRR RR-15301 and the APS by US Department of Energy grant W-31-109-ENG-38.

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M.F.C. designed, performed and analyzed experiments, and wrote the manuscript. D.C.S. designed, performed and analyzed experiments. D.M.D. designed and analyzed experiments. C.R.R.G. designed and performed experiments. R.W.K. designed and analyzed experiments. I.K. designed and performed experiments. B.A.S. advised and assisted on all aspects of the project and wrote the manuscript.

Corresponding authors

Correspondence to Matthew F Calabrese or Brenda A Schulman.

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The authors declare no competing financial interests.

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Supplementary Methods, Supplementary Figures 1–6, and Supplementary Tables 1 and 2 (PDF 13425 kb)

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Calabrese, M., Scott, D., Duda, D. et al. A RING E3–substrate complex poised for ubiquitin-like protein transfer: structural insights into cullin-RING ligases. Nat Struct Mol Biol 18, 947–949 (2011). https://doi.org/10.1038/nsmb.2086

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