Allosteric modulation of adenosine A1 and cannabinoid 1 receptor signaling by G-peptides.

ABSTRACT: While allosteric modulation of GPCR signaling has gained prominence to address the need for receptor specificity, efforts have mainly focused on allosteric sites adjacent to the orthosteric ligand-binding pocket and lipophilic molecules that target transmembrane helices. In this study, we examined the allosteric influence of native peptides derived from the C-terminus of the Gα subunit (G-peptides) on signaling from two Gi-coupled receptors, adenosine A1 receptor (A₁ R) and cannabinoid receptor 1 (CB₁ ). We expressed A₁ R and CB₁ fusions with G-peptides derived from Gαs, Gαi, and Gαq in HEK 293 cells using systematic protein affinity strength modulation (SPASM) and monitored the impact on downstream signaling in the cell compared to a construct l

SUBMITTER: Touma AM 

PROVIDER: S-EPMC7596666 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature