HATRIC-based identification of receptors for orphan ligands

Nadine Sobotzki, Michael A. Schafroth, Alina Rozanova, Anika Koetemann, Florian Marty, Sandra Goetze, Yohei Yamauchi, Erick M. Carreira, Bernd Wollscheid*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

19 Citations (Scopus)
220 Downloads (Pure)

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.

Original languageEnglish
Article number1519
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 17 Apr 2018

Keywords

  • Target identification
  • Chemical tools

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  • Cite this

    Sobotzki, N., Schafroth, M. A., Rozanova, A., Koetemann, A., Marty, F., Goetze, S., Yamauchi, Y., Carreira, E. M., & Wollscheid, B. (2018). HATRIC-based identification of receptors for orphan ligands. Nature Communications, 9, [1519]. https://doi.org/10.1038/s41467-018-03936-z