Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling.
Kilian V M HuberKarin M OlekAndré C MüllerChris Soon Heng TanKeiryn L BennettJacques ColingeGiulio Superti-FurgaPublished in: Nature methods (2015)
Thermal stabilization of proteins after ligand binding provides an efficient means to assess the binding of small molecules to proteins. We show here that in combination with quantitative mass spectrometry, the approach allows for the systematic survey of protein engagement by cellular metabolites and drugs. We profiled the targets of the drugs methotrexate and (S)-crizotinib and the metabolite 2'3'-cGAMP in intact cells and identified the 2'3'-cGAMP cognate transmembrane receptor STING, involved in immune signaling.
Keyphrases
- high resolution
- mass spectrometry
- induced apoptosis
- binding protein
- cell cycle arrest
- drug induced
- liquid chromatography
- high dose
- ms ms
- social media
- cross sectional
- heat shock
- advanced non small cell lung cancer
- protein protein
- endoplasmic reticulum stress
- single cell
- high performance liquid chromatography
- oxidative stress
- cell death
- gas chromatography
- capillary electrophoresis
- small molecule
- low dose
- cell proliferation
- tandem mass spectrometry