Abstract
Significance G protein-coupled receptors (GPCRs) are one of the largest cell surface receptor family that transmit their signal through coupling to intracellular partners, such as G proteins. Receptor oligomerization has been shown to be pivotal in this signaling process. To address how oligomerization can impact on signaling in a major physiological process, dopamine signaling, we used a purified GPCR heteromer composed of the ghrelin and dopamine receptors to which we applied a variety of state-of-the-art biochemical and biophysical approaches. By doing so, we provide a direct experimental evidence for a mechanism where receptor heteromerization affects the conformation of the associated G protein. This sheds light on the way a GPCR oligomer can affect G protein activation to modulate signaling.