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

Nature Structural & Molecular Biology volume 18, pages 947–949 (2011)Cite this article

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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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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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Author notes

  1. Matthew F Calabrese and Daniel C Scott: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
    Matthew F Calabrese, Daniel C Scott, David M Duda, Christy R R Grace, Richard W Kriwacki & Brenda A Schulman
  2. Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
    Daniel C Scott, David M Duda & Brenda A Schulman
  3. Department of Chemistry and Chemical Biology, Cornell University, Northeastern Collaborative Access Team (NE-CAT), Advanced Photon Source (APS), Argonne, Illinois, USA
    Igor Kurinov

Authors

  1. Matthew F Calabrese
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  2. Daniel C Scott
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  3. David M Duda
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  4. Christy R R Grace
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  5. Igor Kurinov
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  6. Richard W Kriwacki
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  7. Brenda A Schulman
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Contributions

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 toMatthew F Calabrese or Brenda A Schulman.

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The authors declare no competing financial interests.

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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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