A Genetically Encoded F-19 NMR Probe Reveals the Allosteric Modulation Mechanism of Cannabinoid Receptor 1
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Inserting unnatural amino acids into the structure of cannabinoid receptor 1 (CB1) can help to illuminate the receptor’s shape-shifting interactions with different biomolecules.
CB1, the main receptor of the psychoactive substance from Cannabis sativa, drives diverse physiological processes in the body and is a promising therapeutic drug target. However, the complex way that the receptor alters its shape and transforms into an active state when it binds with various molecules is not completely understood.
Now, a team that included ShanghaiTech University researchers has shown that changes in the receptor’s shape due to binding can be tracked using fluorine-19 nuclear magnetic resonance (NMR) spectroscopy.
The team demonstrated this by encoding an unnatural amino acid containing a fluorine-19 atom into specific locations in the CB1 structure. The researchers anticipate that the same approach could be used to study the activation of a wide range of other receptor proteins.
- Journal of the American Chemical Society 143, 16320–16325 (2021). doi: 10.1021/jacs.1c06847