Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics
File(s)
Accepted version
Supporting information
Author(s)
Storck Saha, Elisabeth
Morales Sanfrutos, julia
Serwa, remigiusz
Panyain, nattawasdee
Lanyon-Hogg, thomas
Type
Journal Article
Abstract
Post-translational farnesylation or geranylgeranylation at a C-terminal cysteine residue regulates the localization and function of over 100 proteins, including the Ras isoforms, and is a therapeutic target in diseases including cancer and infection. Here, we report global and selective profiling of prenylated proteins in living cells enabled by the development of isoprenoid analogues YnF and YnGG in combination with quantitative chemical proteomics. Eighty prenylated proteins were identified in a single human cell line, 64 for the first time at endogenous abundance without metabolic perturbation. We further demonstrate that YnF and YnGG enable direct identification of post-translationally processed prenylated peptides, proteome-wide quantitative analysis of prenylation dynamics and alternative prenylation in response to four different prenyltransferase inhibitors, and quantification of defective Rab prenylation in a model of the retinal degenerative disease choroideremia.
Date Issued
2019-04-01
Date Acceptance
2019-02-27
Citation
Nature Chemistry, 2019, 11, pp.552-561
ISSN
1755-4330
Publisher
Nature Research
Start Page
552
End Page
561
Journal / Book Title
Nature Chemistry
Volume
11
Copyright Statement
© 2019 The Author(s), under exclusive licence to Springer Nature Limited. The final publication is available at Springer Nature via https://dx.doi.org/10.1038/s41557-019-0237-6
Sponsor
Cancer Research UK
British Heart Foundation
Identifier
https://www.nature.com/articles/s41557-019-0237-6
Grant Number
20183
PG/12/67/29773
Subjects
Science & Technology
Physical Sciences
Chemistry, Multidisciplinary
Chemistry
FARNESYLTRANSFERASE INHIBITORS
WIDE ANALYSIS
TARGET
FARNESYLATION
PRENYLOME
RAS
IDENTIFICATION
DEGENERATION
LIPIDATION
PROTEOMICS
Adaptor Proteins, Signal Transducing
Alkynes
Animals
Cell Line
Gene Knockout Techniques
Humans
Mass Spectrometry
Mice, Knockout
Molecular Probes
Protein Prenylation
Proteins
Proteome
Proteomics
Cell Line
Animals
Mice, Knockout
Humans
Alkynes
Adaptor Proteins, Signal Transducing
Proteins
Proteome
Molecular Probes
Proteomics
Mass Spectrometry
Protein Prenylation
Gene Knockout Techniques
Organic Chemistry
03 Chemical Sciences
Publication Status
Published
Date Publish Online
2019-04-01