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HATRIC-based identification of receptors for orphan ligands

Author

Listed:
  • Nadine Sobotzki

    (ETH Zurich
    Merck Ventures B. V.)

  • Michael A. Schafroth

    (ETH Zürich)

  • Alina Rudnicka

    (Institute of Molecular Life Sciences
    University Walk)

  • Anika Koetemann

    (ETH Zurich)

  • Florian Marty

    (Dualsystems Biotech AG
    Biognosys AG)

  • Sandra Goetze

    (ETH Zurich)

  • Yohei Yamauchi

    (University Walk)

  • Erick M. Carreira

    (ETH Zürich)

  • Bernd Wollscheid

    (ETH Zurich)

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.

Suggested Citation

  • Nadine Sobotzki & Michael A. Schafroth & Alina Rudnicka & Anika Koetemann & Florian Marty & Sandra Goetze & Yohei Yamauchi & Erick M. Carreira & Bernd Wollscheid, 2018. "HATRIC-based identification of receptors for orphan ligands," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03936-z
    DOI: 10.1038/s41467-018-03936-z
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    Cited by:

    1. Maik Müller & Fabienne Gräbnitz & Niculò Barandun & Yang Shen & Fabian Wendt & Sebastian N. Steiner & Yannik Severin & Stefan U. Vetterli & Milon Mondal & James R. Prudent & Raphael Hofmann & Marc Oos, 2021. "Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Jiangnan Zheng & Zhendong Zheng & Changying Fu & Yicheng Weng & An He & Xueting Ye & Weina Gao & Ruijun Tian, 2023. "Deciphering intercellular signaling complexes by interaction-guided chemical proteomics," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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