English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Insights into ubiquitin chain architecture using Ub-clipping

Swatek, K. N., Usher, J. L., Kueck, A. F., Gladkova, C., Mevissen, T. E. T., Pruneda, J. N., et al. (2019). Insights into ubiquitin chain architecture using Ub-clipping. NATURE, 572(7770), 533-537. doi:10.1038/s41586-019-1482-y.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Swatek, Kirby N.1, Author           
Usher, Joanne L.2, Author
Kueck, Anja F.2, Author
Gladkova, Christina2, Author
Mevissen, Tycho E. T.2, Author
Pruneda, Jonathan N.2, Author
Skern, Tim2, Author
Komander, David2, Author
Affiliations:
1Schulman, Brenda / Molecular Machines and Signaling, Max Planck Institute of Biochemistry, Max Planck Society, ou_2466699              
2external, ou_persistent22              

Content

show
hide
Free keywords: SPECTROMETRY ENABLES CHARACTERIZATION; MOLECULAR-BASIS; PARKIN; POLYUBIQUITIN; COMPLEX; PHOSPHORYLATION; MECHANISM; REVEALS; ACETYLATION; SPECIFICITYScience & Technology - Other Topics;
 Abstract: Protein ubiquitination is a multi-functional post-translational modification that affects all cellular processes. Its versatility arises from architecturally complex polyubiquitin chains, in which individual ubiquitin moieties may be ubiquitinated on one or multiple residues, and/or modified by phosphorylation and acetylation(1-3). Advances in mass spectrometry have enabled the mapping of individual ubiquitin modifications that generate the ubiquitin code; however, the architecture of polyubiquitin signals has remained largely inaccessible. Here we introduce Ub-clipping as a methodology by which to understand polyubiquitin signals and architectures. Ub-clipping uses an engineered viral protease, Lb(pro)*, to incompletely remove ubiquitin from substrates and leave the signature C-terminal GlyGly dipeptide attached to the modified residue; this simplifies the direct assessment of protein ubiquitination on substrates and within polyubiquitin. Monoubiquitin generated by Lb(pro)* retains GlyGly-modified residues, enabling the quantification of multiply GlyGly-modified branch-point ubiquitin. Notably, we find that a large amount (10-20%) of ubiquitin in polymers seems to exist as branched chains. Moreover, Ub-clipping enables the assessment of co-existing ubiquitin modifications. The analysis of depolarized mitochondria reveals that PINK1/parkin-mediated mitophagy predominantly exploits mono- and short-chain polyubiquitin, in which phosphorylated ubiquitin moieties are not further modified. Ub-clipping can therefore provide insight into the combinatorial complexity and architecture of the ubiquitin code.

Details

show
hide
Language(s): eng - English
 Dates: 2019
 Publication Status: Published in print
 Pages: 21
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000482219600047
DOI: 10.1038/s41586-019-1482-y
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: NATURE
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Pages: - Volume / Issue: 572 (7770) Sequence Number: - Start / End Page: 533 - 537 Identifier: ISSN: 0028-0836