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

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

Author information

1
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore, 117543, Singapore.
2
Department of Biological Sciences, National University of Singapore, Singapore.
3
Institute of Bioengineering, Zhejiang University of Technology, China.
4
Department of Biological Chemistry, University of Science & Technology, South Korea.

Abstract

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

PMID:
28429463
DOI:
10.1002/anie.201702509

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