title: Proteome-wide drug and metabolite interaction mapping by thermal-stability profiling.
abstract: 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.
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Kilian V M
authors.identifier: http://orcid.org/0000-0002-1103-5300
authors.initials: KV
authors.lastname: Huber
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Olek
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: André C
authors.initials: AC
authors.lastname: Müller
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Chris Soon Heng
authors.initials: CS
authors.lastname: Tan
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Keiryn L
authors.initials: KL
authors.lastname: Bennett
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
authors.forename: Jacques
authors.initials: J
authors.lastname: Colinge
authors.affiliation: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.|Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Giulio
authors.identifier: http://orcid.org/0000-0002-0570-1768
authors.initials: G
authors.lastname: Superti-Furga
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D019295:Computational Biology; D000077547:Crizotinib; D015195:Drug Design; D006801:Humans; D007107:Immune System; D020014:K562 Cells; D008024:Ligands; D013058:Mass Spectrometry; D008727:Methotrexate / Q000737:chemistry; D051379:Mice; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D011720:Pyrazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D015398:Signal Transduction; D049490:Systems Biology; D013696:Temperature
chemical_list: D002352:Carrier Proteins; D008024:Ligands; D047428:Protein Kinase Inhibitors; D020543:Proteome; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; D008727:Methotrexate