2016/11/09 by Punita Kumari, Ashish Srivastava, Ramanuj Banerjee +8 · 2 citations
Biochemistry, Genetics and Molecular Biology · Neuroscience · Medicine · #Receptor Mechanisms and Signaling #Neuropeptides and Animal Physiology #Monoclonal and Polyclonal Antibodies Research
paper · pdf · doi:10.1038/ncomms13416
openalex publication_date 2016/11/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Abstract G Protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors and drug targets. GPCR signalling and desensitization is critically regulated by β-arrestins (βarr). GPCR–βarr interaction is biphasic where the phosphorylated carboxyl terminus of GPCRs docks to the N-domain of βarr first and then seven transmembrane core of the receptor engages with βarr. It is currently unknown whether fully engaged GPCR–βarr complex is essential for functional outcomes or partially engaged complex can also be functionally competent. Here we assemble partially and fully engaged complexes of a chimeric β 2 V 2 R with βarr1, and discover that the core interaction is dispensable for receptor endocytosis, ERK MAP kinase binding and activation. Furthermore, we observe that carvedilol, a βarr biased ligand, does not promote detectable engagement between βarr1 and the receptor core. These findings uncover a previously unknown aspect of GPCR-βarr interaction and provide novel insights into GPCR signalling and regulatory paradigms.