Differential manipulation of arrestin-3 binding to basal and agonist-activated G protein-coupled receptors.

ABSTRACT: Non-visual arrestins interact with hundreds of different G protein-coupled receptors (GPCRs). Here we show that by introducing mutations into elements that directly bind receptors, the specificity of arrestin-3 can be altered. Several mutations in the two parts of the central "crest" of the arrestin molecule, middle-loop and C-loop, enhanced or reduced arrestin-3 interactions with several GPCRs in receptor subtype and functional state-specific manner. For example, the Lys139Ile substitution in the middle-loop dramatically enhanced the binding to inactive M₂ muscarinic receptor, so that agonist activation of the M₂ did not further increase arrestin-3 binding. Thus, the Lys139Ile mutation made arrestin-3 essentially an activation-independent binding partner of M_2</

SUBMITTER: Prokop S 

PROVIDER: S-EPMC5797668 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature