Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks
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Date
2021-12
Publication Type
Journal Article
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yes
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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.
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published
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Volume
12 (1)
Pages / Article No.
7036
Publisher
Nature
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Organisational unit
03625 - Oxenius, Annette / Oxenius, Annette
03651 - Loessner, Martin / Loessner, Martin
09595 - Snijder, Berend (ehemalig) / Snijder, Berend (former)
03861 - Bode, Jeffrey W. / Bode, Jeffrey W.
02072 - Proteomics Plattform D-HEST
02072 - Proteomics Plattform D-HEST
Notes
Funding
ETH-30 17-1 - Light-mediated proximity detection of dynamic protein interactions (ETHZ)
ETH-25 15-2 - Diversity and plasticity of synaptic cleft proteotypes (ETHZ)
160259 - Direct identification of lateral protein interactions in the plasma membrane of living cells and tissues (SNF)
ETH-25 15-2 - Diversity and plasticity of synaptic cleft proteotypes (ETHZ)
160259 - Direct identification of lateral protein interactions in the plasma membrane of living cells and tissues (SNF)