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Global profiling of co- and post-translationally N-myristoylated proteomes in human cells

Author

Listed:
  • Emmanuelle Thinon

    (Imperial College London
    Imperial College London
    Present address: The Rockefeller University, 1230 York Avenue, New York, New York, USA)

  • Remigiusz A. Serwa

    (Imperial College London)

  • Malgorzata Broncel

    (Imperial College London)

  • James A. Brannigan

    (York Structural Biology Laboratory, University of York)

  • Ute Brassat

    (Imperial College London
    Imperial College London
    Present address: EUFETS GmbH, Vollmersbachstrasse 66, 55743 Idar-Oberstein, Germany)

  • Megan H. Wright

    (Imperial College London
    Institute of Chemical Biology, Imperial College London
    Present address: Department of Chemistry, TU München, Lichtenbergstrasse 4, D-85748 Garching, Germany)

  • William P. Heal

    (Imperial College London
    Present address: Department of Chemistry, Kings College London, London SE1 1UL, UK)

  • Anthony J. Wilkinson

    (York Structural Biology Laboratory, University of York)

  • David J. Mann

    (Imperial College London
    Institute of Chemical Biology, Imperial College London)

  • Edward W. Tate

    (Imperial College London
    Institute of Chemical Biology, Imperial College London)

Abstract

Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development and progression of a range of human diseases. Here, we report the global N-myristoylated proteome in human cells determined using quantitative chemical proteomics combined with potent and specific human N-myristoyltransferase (NMT) inhibition. Global quantification of N-myristoylation during normal growth or apoptosis allowed the identification of >100 N-myristoylated proteins, >95% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for >70 substrates simultaneously across the proteome. Small-molecule inhibition through a conserved substrate-binding pocket is also demonstrated by solving the crystal structures of inhibitor-bound NMT1 and NMT2. The presented data substantially expand the known repertoire of co- and post-translational N-myristoylation in addition to validating tools for the pharmacological inhibition of NMT in living cells.

Suggested Citation

  • Emmanuelle Thinon & Remigiusz A. Serwa & Malgorzata Broncel & James A. Brannigan & Ute Brassat & Megan H. Wright & William P. Heal & Anthony J. Wilkinson & David J. Mann & Edward W. Tate, 2014. "Global profiling of co- and post-translationally N-myristoylated proteomes in human cells," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5919
    DOI: 10.1038/ncomms5919
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