Transfer of ubiquitin protein caught in the act

Deshaies, Raymond J.; Pierce, Nathan W.

doi:10.1038/d41586-020-00325-9

NEWS AND VIEWS
12 February 2020

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.

Raymond J. Deshaies ⁰ &
Nathan W. Pierce ¹

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

You can also search for this author in PubMed Google Scholar
Nathan W. Pierce
1. Nathan W. Pierce is at Amgen Research, Amgen, South San Francisco, California 94080, USA.
View author publications

You can also search for this author in PubMed Google Scholar

Access through your institution

Buy or subscribe

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.

Access options

Access through your institution

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Nature 578, 372-373 (2020)

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

References

Lydeard, J. R., Schulman, B. A. & Harper, J. W. EMBO Rep. 14, 1050–1061 (2013).
PubMed Article Google Scholar
Saha, A. & Deshaies, R. J. Mol. Cell 32, 21–31 (2008).
PubMed Article Google Scholar
Duda, D. M. et al. Cell 134, 995–1006 (2008)
PubMed Article Google Scholar
Read, M. A. et al. Mol. Cell. Biol. 20, 2326–2333 (2000).
PubMed Article Google Scholar
Podust, V. N. et al. Proc. Natl Acad. Sci. USA 97, 4579–4584 (2000).
PubMed Article Google Scholar
Baek, K. et al. Nature 578, 461–466 (2020).
Article Google Scholar
Zheng, N. et al. Nature 416, 703–709 (2002).
PubMed Article Google Scholar
Cui, J. et al. Science 329, 1215–1218 (2010).
PubMed Article Google Scholar
Sakata, E. et al. Nature Struct. Mol. Biol. 14, 167–168 (2007).
PubMed Article Google Scholar
Scott, D. C. et al. Cell 166, 1198–1214 (2016).
PubMed Article Google Scholar
Sievers, Q. L., Gasser, J. A., Cowley, G. S., Fischer, E. S. & Ebert, B. L. Blood 132, 1293–1303 (2018).
PubMed Article Google Scholar
Verma, R., Mohl, D. & Deshaies, D. J. Mol. Cell https://doi.org/10.1016/j.molcel.2020.01.010 (2020).
Article Google Scholar
Smith, B. E. et al. Nature Commun. 10, 131 (2019).
PubMed Article Google Scholar