Global Mapping of Protein-Lipid Interactions by Using Modified Choline-Containing Phospholipids Metabolically Synthesized in Live Cells

Angew Chem Int Ed Engl. 2017 May 15;56(21):5829-5833. doi: 10.1002/anie.201702509. Epub 2017 Apr 21.


The protein-lipid interaction is an essential metabolic process that mediates cellular signaling and functions. Existing strategies for large-scale mapping studies of the protein-lipid interaction fall short in their incompatibility with metabolic incorporation or inability to remove unwanted interferences from lipidated proteins. By incorporating an alkyne-containing choline head group and a diazirine-modified fatty acid simultaneously into choline-containing phospholipids synthesized from live mammalian cells, protein-phospholipid interactions have been successfully imaged in live cells. Subsequent in situ profiling of the modified Cho phospholipid-crosslinked proteins followed by quantitative proteomics allowed identification of several hundred putative phospholipid-interacting proteins, some of which were further validated.

Keywords: click chemistry; phosphatidylcholine; photo-crosslinking; protein-lipid interactions; quantitative proteomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Choline / chemistry*
  • Chromatography, Liquid
  • Humans
  • Lipids / chemistry*
  • Mass Spectrometry
  • Phospholipids / chemistry*
  • Proteins / chemistry*
  • Proteomics*


  • Lipids
  • Phospholipids
  • Proteins
  • Choline