HATRIC-based identification of receptors for orphan ligands

Nadine Sobotzki, Michael A. Schafroth, Alina Rudnicka, Anika Koetemann, Florian Marty, Sandra Goetze, Yohei Yamauchi, Erick M. Carreira and Bernd Wollscheid ()
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Nadine Sobotzki: ETH Zurich
Michael A. Schafroth: ETH Zürich
Alina Rudnicka: Institute of Molecular Life Sciences
Anika Koetemann: ETH Zurich
Florian Marty: Dualsystems Biotech AG
Sandra Goetze: ETH Zurich
Yohei Yamauchi: University Walk
Erick M. Carreira: ETH Zürich
Bernd Wollscheid: ETH Zurich

Nature Communications, 2018, vol. 9, issue 1, 1-8

Abstract: Abstract Cellular responses depend on the interactions of extracellular ligands, such as nutrients, growth factors, or drugs, with specific cell-surface receptors. The sensitivity of these interactions to non-physiological conditions, however, makes them challenging to study using in vitro assays. Here we present HATRIC-based ligand receptor capture (HATRIC-LRC), a chemoproteomic technology that successfully identifies target receptors for orphan ligands on living cells ranging from small molecules to intact viruses. HATRIC-LRC combines a click chemistry-based, protein-centric workflow with a water-soluble catalyst to capture ligand-receptor interactions at physiological pH from as few as 1 million cells. We show HATRIC-LRC utility for general antibody target validation within the native nanoscale organization of the surfaceome, as well as receptor identification for a small molecule ligand. HATRIC-LRC further enables the identification of complex extracellular interactomes, such as the host receptor panel for influenza A virus (IAV), the causative agent of the common flu.

Date: 2018
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DOI: 10.1038/s41467-018-03936-z

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