A chemogenetic strategy for inhibiting G protein-coupled receptor activity using metal coordination

Abstract G protein-coupled receptors regulate diverse physiological functions in mammalian cells. Methods enabling temporal control of individual G protein-coupled receptor activity are highly desirable for dissecting their specific functions. Here, we report a chemogenetic strategy for inhibiting adenosine A2A receptor activity. By introducing a histidine mutation to A2A receptor, receptor activity was suppressed in a CuCl2-dependent manner. Notably, this approach was successfully extended to another G protein-coupled receptor family member, highlighting its potential as a versatile tool for functional studies across various G protein-coupled receptors.