Issue 6, 2021

Activation of a G protein-coupled receptor through indirect antibody-mediated tethering of ligands

Abstract

Antibodies raised against many cell surface proteins, including G protein-coupled receptors, remain important tools for their functional characterization. By linking antibodies to ligands for cell surface proteins, such adducts can be targeted to the surface of a cell type of choice. Site-specific functionalization of full-size antibodies with synthetic moieties remains challenging. Here we present new approaches in which single domain antibodies (known as VHHs or nanobodies) that target either cell surface proteins or conventional antibodies are used to indirectly deliver ligands for GPCRs to their sites of action. The combination of high yield production of nanobodies, facile site-specific functionalization, and compatibility with commercially available mouse and rabbit antibodies should enable wide application of this approach.

Graphical abstract: Activation of a G protein-coupled receptor through indirect antibody-mediated tethering of ligands

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Article information

Article type
Paper
Submitted
24 5 2021
Accepted
01 10 2021
First published
11 10 2021
This article is Open Access
Creative Commons BY-NC license

RSC Chem. Biol., 2021,2, 1692-1700

Activation of a G protein-coupled receptor through indirect antibody-mediated tethering of ligands

R. W. Cheloha, F. A. Fischer, T. J. Gardella and H. L. Ploegh, RSC Chem. Biol., 2021, 2, 1692 DOI: 10.1039/D1CB00118C

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