Research Article

Microenvironment mapping via Dexter energy transfer on immune cells

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Science  06 Mar 2020:
Vol. 367, Issue 6482, pp. 1091-1097
DOI: 10.1126/science.aay4106

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Pinpointing proteins

To develop drugs that target a specific cell surface protein, it's helpful to know which other proteins reside in its vicinity. Geri et al. report a light-triggered labeling technique that improves the spatial resolution for this type of mapping. Specifically, they rely on a photocatalyst with a very short energy-transfer range to activate a carbene-based label that can only diffuse a short distance in water before reacting. They showcase the technique by mapping the environment of the programmed-death ligand 1 (PDL1) protein on B cell surfaces, a system of considerable interest in cancer immunotherapy.

Science, this issue p. 1091

Abstract

Many disease pathologies can be understood through the elucidation of localized biomolecular networks, or microenvironments. To this end, enzymatic proximity labeling platforms are broadly applied for mapping the wider spatial relationships in subcellular architectures. However, technologies that can map microenvironments with higher precision have long been sought. Here, we describe a microenvironment-mapping platform that exploits photocatalytic carbene generation to selectively identify protein-protein interactions on cell membranes, an approach we term MicroMap (μMap). By using a photocatalyst-antibody conjugate to spatially localize carbene generation, we demonstrate selective labeling of antibody binding targets and their microenvironment protein neighbors. This technique identified the constituent proteins of the programmed-death ligand 1 (PD-L1) microenvironment in live lymphocytes and selectively labeled within an immunosynaptic junction.

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