Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics

Elisabeth M. Storck, Julia Morales-Sanfrutos, Remigiusz A. Serwa, Nattawadee Panyain, Thomas Lanyon-Hogg, Tanya Tolmachova, Leandro N. Ventimiglia, Juan Martin-Serrano, Miguel C. Seabra, Beata Wojciak-Stothard, Edward W. Tate

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)552-561
Number of pages10
JournalNature Chemistry
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2019

Keywords

  • FARNESYLTRANSFERASE INHIBITORS
  • WIDE ANALYSIS
  • TARGET
  • FARNESYLATION
  • PRENYLOME
  • RAS
  • IDENTIFICATION
  • DEGENERATION
  • LIPIDATION
  • PROTEOMICS

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