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

G protein-coupled receptors (GPCRs) regulate diverse physiological functions in mammalian cells. Methods enabling temporal control of individual GPCR activity are highly desirable for dissecting their specific functions. Here, we report a chemogenetic strategy for inhibiting adenosine A2A receptor (A2AR) activity. By introducing a histidine mutation to A2AR, receptor activity was suppressed in a CuCl2-dependent manner. Notably, this approach was successfully extended to another GPCR family member, highlighting its potential as a versatile tool for functional studies across various GPCRs.