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Transfer of ubiquitin protein caught in the act

A process termed ubiquitination mediates the regulated destruction of cellular proteins, thereby preventing disease or infection. Structural data now reveal how a crucial regulator of ubiquitination enzymes coordinates this process.
  1. Raymond J. Deshaies

    1. Raymond J. Deshaies is at Amgen Research, Amgen, Thousand Oaks, California 91320, USA.

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  2. Nathan W. Pierce

    1. Nathan W. Pierce is at Amgen Research, Amgen, South San Francisco, California 94080, USA.

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Many cellular functions that occur in eukaryotes (organisms whose cells contain a nucleus) are regulated by targeted protein destruction. This targeting is often achieved by a process called ubiquitination (or ubiquitylation), in which a protein selected for destruction is tagged with the protein ubiquitin. Ubiquitination is aided by enzymes known as E3 ligases, a subset of which are called cullin–RING ubiquitin ligases (CRLs)1. CRLs help to transfer ubiquitin from an E2 conjugating enzyme, to which it is bound, onto the target protein1. By default, CRLs are inactive, and they are activated when a protein called NEDD8 (which is similar in sequence to ubiquitin) becomes attached to the cullin subunit of the CRL2–5. But how this activation happens has been a mystery. Writing in Nature, Baek et al.6 report structural data obtained using a technique called cryo-electron microscopy (cryo-EM) that fills in some of the blanks.

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Nature 578, 372-373 (2020)

doi: https://doi.org/10.1038/d41586-020-00325-9

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Competing Interests

Both R.J.D. and N.W.P. are employees of Amgen. R.J.D. is in addition an officer of the corporation.

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