Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks

Proteomics 0301 basic medicine Immunological Synapses Light Science Antigen-Presenting Cells Gene Expression HL-60 Cells Receptors, Cell Surface Cell Communication CD8-Positive T-Lymphocytes Ligands Lymphocyte Activation Article Antibodies 03 medical and health sciences Cell Line, Tumor Humans Precision Medicine B-Lymphocytes Biological Products Q 3. Good health Optogenetics Chromatography, Liquid Protein Binding
DOI: 10.1038/s41467-021-27280-x Publication Date: 2021-12-02T11:03:04Z
ABSTRACT
AbstractThe 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.
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