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

ABSTRACT: Delineating the extracellular interaction network of the cell surface proteotype (the surfaceome) is fundamental to understanding cellular signaling function in health and disease. Here, we developed LUX-MS, an optoproteomic technology that enables the spatiotemporal and proteome-wide study of surfaceome signaling architectures at nanoscale level without the need for genetic manipulation. A tunable, light-triggered singlet oxygen generator (SOG) based mechanism mediates in-situ proximity-tagging for subsequent mass spectrometry-based identification of acute protein interactions in their native cellular context. We applied LUX-MS to the characterization of surfaceome signaling structures engaged by antibodies, small molecule drugs, biologics and intact bacteriophages across organisms and in complex environments. Cell-type resolved dissection of intercellular communication using LUX-MS thereby revealed the molecular architecture of functional immunological signaling synapses in unprecedented detail. Altogether, LUX-MS enables facebooking of the social protein networks within surfaceome signaling architectures and provides an unprecedented molecular framework for the rational design of biomedical intervention strategies.

INSTRUMENT(S):

ORGANISM(S): Listeria Phage A500 Homo Sapiens (human) Escherichia Coli Listeria Monocytogenes Serotype 4b Mus Musculus (mouse)

TISSUE(S): B Cell, Primary Cell, Blood Cell, Cell Suspension Culture, T Cell, Dendritic Cell, Cell Culture

DISEASE(S): Lymphoma

SUBMITTER: Maik Müller  

LAB HEAD: Bernd Wollscheid

PROVIDER: PXD020481 | Pride | 2021-06-14

REPOSITORIES: Pride