Linkage-Specific Ubiquitin Chain Formation Depends on a Lysine Hydrocarbon Ruler
Document Type
Article
Publication Date
1-1-2020
Publication Title
Nature Chemical Biology
Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. 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.]
Disciplines
Biochemistry
Language
English
Repository Citation
Liwocha, J.,
Krist, D.,
van der Heden van Noort, G.,
Hansen, F.,
Truong, V.,
Karayel, O.,
Purser, N.,
Houston, D.,
Burton, N.,
Bostock, M.,
Sattler, M.,
Mann, M.,
Harrison, J.,
Kleiger, G.,
Ovaa, H.,
Schulman, B.
(2020).
Linkage-Specific Ubiquitin Chain Formation Depends on a Lysine Hydrocarbon Ruler.
Nature Chemical Biology
http://dx.doi.org/10.1038/s41589-020-00696-0