Chemogenetic Approach Using Ni(II) Complex-Agonist Conjugates Allows Selective Activation of Class A G-Protein-Coupled Receptors.

ABSTRACT: Investigating individual G-protein-coupled receptors (GPCRs) involved in various signaling cascades can unlock a myriad of invaluable physiological findings. One of the promising strategies for addressing the activity of each subtype of receptor is to design chemical turn-on switches on the target receptors. However, valid methods to selectively control class A GPCRs, the largest receptor family encoded in the human genome, remain limited. Here, we describe a novel approach to chemogenetically manipulate activity of engineered class A GPCRs carrying a His₄ tag, using metal complex-agonist conjugates (MACs). This manipulation is termed coordination tethering. With the assistance of coordination bonds, MACs showed 10-100-fold lower EC₅₀ values in the engineered receptor

SUBMITTER: Kubota R 

PROVIDER: S-EPMC6161059 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature