Fusion with Promiscuous Gα₁₆ Subunit Reveals Signaling Bias at Muscarinic Receptors.

ABSTRACT: A complex evaluation of agonist bias at G-protein coupled receptors at the level of G-protein classes and isoforms including non-preferential ones is essential for advanced agonist screening and drug development. Molecular crosstalk in downstream signaling and a lack of sufficiently sensitive and selective methods to study direct coupling with G-protein of interest complicates this analysis. We performed binding and functional analysis of 11 structurally different agonists on prepared fusion proteins of individual subtypes of muscarinic receptors and non-canonical promiscuous α-subunit of G₁₆ protein to study agonist bias. We have demonstrated that fusion of muscarinic receptors with Gα₁₆ limits access of other competitive Gα subunits to the receptor, and thus enables

SUBMITTER: Randakova A 

PROVIDER: S-EPMC8469978 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature