Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler
ORCID
Joseph Harrison: 0000-0002-2118-6524
Document Type
Article
Publication Title
Nature Chemical Biology
Department
Chemistry
ISSN
1552-4450
Volume
17
Issue
3
DOI
10.1038/s41589-020-00696-0
First Page
272
Last Page
279
Publication Date
3-1-2021
Abstract
Virtually all aspects of cell biology are regulated by a ubiquitin code where distinct ubiquitin chain architectures guide the binding events and itineraries of modified substrates. Various combinations of E2 and E3 enzymes accomplish chain formation by forging isopeptide bonds between the C terminus of their transiently linked donor ubiquitin and a specific nucleophilic amino acid on the acceptor ubiquitin, yet it is unknown whether the fundamental feature of most acceptors—the lysine side chain—affects catalysis. Here, use of synthetic ubiquitins with non-natural acceptor site replacements reveals that the aliphatic side chain specifying reactive amine geometry is a determinant of the ubiquitin code, through unanticipated and complex reliance of many distinct ubiquitin-carrying enzymes on a canonical acceptor lysine. [Figure not available: see fulltext.]
Recommended Citation
Liwocha, J.,
Krist, D. T.,
van der Heden van Noort, G. J.,
Hansen, F. M.,
Truong, V. H.,
Karayel, O.,
Purser, N.,
Houston, D.,
Burton, N.,
Bostock, M. J.,
Sattler, M.,
Mann, M.,
Harrison, J. S.,
Kleiger, G.,
Ovaa, H.,
&
Schulman, B. A.
(2021).
Linkage-specific ubiquitin chain formation depends on a lysine hydrocarbon ruler.
Nature Chemical Biology, 17(3), 272–279.
DOI: 10.1038/s41589-020-00696-0
https://scholarlycommons.pacific.edu/cop-facarticles/833
Comments
Funding Sponsor: National Institute of Health, 201302640