1. Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks
- Author
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Milon Mondal, Fabian Wendt, Alexey I. Nesvizhskii, Bernd Wollscheid, Roman C. Sarott, Marc van Oostrum, Jeffrey W. Bode, Yannik Severin, Annette Oxenius, Maik Müller, Fabienne Gräbnitz, Sebastian N. Steiner, Martin J. Loessner, Niculò Barandun, John A. Robinson, Yang Shen, Stefan U. Vetterli, Berend Snijder, James R. Prudent, Erick M. Carreira, and Raphael Hofmann
- Subjects
Proteomics ,Immunological Synapses ,Light ,General Physics and Astronomy ,Gene Expression ,Drug action ,Cell Communication ,CD8-Positive T-Lymphocytes ,Ligands ,Lymphocyte Activation ,0302 clinical medicine ,Tandem Mass Spectrometry ,Precision Medicine ,Receptor ,0303 health sciences ,B-Lymphocytes ,Multidisciplinary ,Singlet Oxygen ,Chemistry ,Small molecule ,Cell biology ,Protein-protein interaction networks ,medicine.anatomical_structure ,Target protein ,Protein Binding ,Signal Transduction ,Cell signaling ,T cell ,Science ,Antigen-Presenting Cells ,HL-60 Cells ,Receptors, Cell Surface ,General Biochemistry, Genetics and Molecular Biology ,Antibodies ,Article ,Protein–protein interaction ,Small Molecule Libraries ,03 medical and health sciences ,Cell surface receptor ,Cell Line, Tumor ,Target identification ,medicine ,Humans ,030304 developmental biology ,Biological Products ,Virion ,General Chemistry ,Optogenetics ,Extracellular signalling molecules ,Chemical tools ,030217 neurology & neurosurgery ,Chromatography, Liquid - Abstract
The molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target protein communities and the possibility to engineer extracellular signaling. Here, we develop an optoproteomic technology termed LUX-MS that enables the targeted elucidation of acute protein interactions on and in between living cells using light-controlled singlet oxygen generators (SOG). By using SOG-coupled antibodies, small molecule drugs, biologics and intact viral particles, we demonstrate the ability of LUX-MS to decode ligand receptor interactions across organisms and to discover surfaceome receptor nanoscale organization with direct implications for drug action. Furthermore, by coupling SOG to antigens we achieved light-controlled molecular mapping of intercellular signaling within functional immune synapses between antigen-presenting cells and CD8+ T cells providing insights into T cell activation with spatiotemporal specificity. LUX-MS based decoding of surfaceome signaling architectures thereby provides a molecular framework for the rational development of theranostic strategies., Nature Communications, 12 (1), ISSN:2041-1723
- Published
- 2021