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Updated: Mar 30, 2026

Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
Published on: September 13, 2013
In-Membrane Chemical Modification (IMCM) for Site-Specific Chromophore Labeling of GPCRs
Lukas Sušac1, Casey O'Connor1,2, Raymond C Stevens2
1Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA).
Abstract:
We present in-membrane chemical modification (IMCM) for obtaining selective chromophore labeling of intracellular surface cysteines in G-protein-coupled receptors (GPCRs) with minimal mutagenesis. This method takes advantage of the natural protection of most cysteines by the membrane environment. Practical use of IMCM is illustrated with the site-specific introduction of chromophores for NMR and fluorescence spectroscopy in the human κ-opioid receptor (KOR) and the human A2A adenosine receptor (A2A AR). IMCM is applicable to a wide range of in vitro studies of GPCRs, including single-molecule spectroscopy, and is a promising platform for in-cell spectroscopy experiments.
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