Experimental and computational analysis of biased agonism on full-length and a C-terminally truncated adenosine A_2A receptor.

ABSTRACT: Biased agonism, the ability of agonists to differentially activate downstream signaling pathways by stabilizing specific receptor conformations, is a key issue for G protein-coupled receptor (GPCR) signaling. The C-terminal domain might influence this functional selectivity of GPCRs as it engages G proteins, GPCR kinases, β-arrestins, and several other proteins. Thus, the aim of this paper is to compare the agonist-dependent selectivity for intracellular pathways in a heterologous system expressing the full-length (A_2AR) and a C-tail truncated (A_2A ^Δ40R lacking the last 40 amino acids) adenosine A_2A receptor, a GPCR that is already targeted in Parkinson's disease using a first-in-class drug. Experimental data such as ligand binding, cAMP producti

SUBMITTER: Navarro G 

PROVIDER: S-EPMC7550916 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature