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New insights into ubiquitin E3 ligase mechanism

Nature Structural & Molecular Biology volume 21, pages 301–307 (2014)Cite this article

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Abstract

E3 ligases carry out the final step in the ubiquitination cascade, catalyzing transfer of ubiquitin from an E2 enzyme to form a covalent bond with a substrate lysine. Three distinct classes of E3 ligases have been identified that stimulate transfer of ubiquitin and ubiquitin-like proteins through either a direct or an indirect mechanism. Only recently have the catalytic mechanisms of E3 ligases begun to be elucidated.

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Figure 1: RING E3 ligases.
Figure 2: Mechanism by which RING E3s stimulate ubiquitin transfer.
Figure 3: E2 back-side binding by additional domains in RING E3 ligases.
Figure 4: HECT E3 ligases.
Figure 5: RBR E3 ligase mechanism.

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Acknowledgements

We thank R. Hay, A. Plechanovová and B. Schulman for providing coordinates of modeled complexes. C.W. acknowledges grant support from the US National Institutes of Health (GM095822) and National Science Foundation (MCB0920082).

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  1. Department of Chemistry and Biochemistry, James Madison University, Harrisonburg, Virginia, USA

    Christopher E Berndsen

  2. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Cynthia Wolberger

  3. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Cynthia Wolberger

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Correspondence to Cynthia Wolberger.

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Berndsen, C., Wolberger, C. New insights into ubiquitin E3 ligase mechanism. Nat Struct Mol Biol 21, 301–307 (2014). https://doi.org/10.1038/nsmb.2780

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