Title

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.]

Comments

Funding Sponsor: National Institute of Health, 201302640

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