A nanoscale map of the human cell surface proteome reveals spatial and functional organization.

Proximity labeling of 85 antigens on human T lymphocytes and B lymphoblasts reveals functional modules and spatial organization of the cell surface proteome, including widely dispersed versus localized antigens.

• Why it matters: Cell-surface proteins control development, immunity, and disease, but their large-scale spatial organization is not well characterized, limiting mechanistic understanding.
• What they did: The study used proximity labeling of 85 antigens combined with data-independent acquisition mass spectrometry to map surface proteins, then applied spatial modeling and a machine learning classifier to predict surface protein associations.
• The result: It identifies mitochondrial proteins at the surface and links IL-10 receptor beta subunit regulation to type I interferon signaling, providing a resource to explore spatial and functional organization.

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