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Updated: Jul 11, 2026

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
Published on: June 28, 2019
Interaction of a fragment of the cannabinoid CB1 receptor C-terminus with arrestin-2
Kunal Bakshi1, Richard W Mercier, Spiro Pavlopoulos
1Department of Pharmaceutical Sciences, University of Connecticut, 69 North Eagleville Road, U-3092, Storrs, CT 06269, USA.
Abstract:
Desensitization of the cannabinoid CB1 receptor is mediated by the interaction with arrestin. In this study, we report the structural changes of a synthetic diphosphorylated peptide corresponding to residues 419-439 of the CB1 C-terminus upon binding to arrestin-2. This segment is pivotal to the desensitization of CB1. Using high-resolution proton NMR, we observe two helical segments in the bound peptide that are separated by the presence a glycine residue. The binding we observe is with a diphoshorylated peptide, whereas a previous study reported binding of a highly phosphorylated rhodopsin fragment to visual arrestin. The arrestin bound conformations of the peptides are compared.
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