Assays using arrestin recruitment and unmodified receptors

A method for identifying an agonist or an antagonist of a G protein-coupled receptor, comprising:

• a. providing a first polypeptide comprising the amino acid sequence of SEQ ID NO:
• 2, said first polypeptide is conjugated to a first protein, wherein the first protein is selected from the group consisting of arrestin and G-protein coupled receptor kinase (GRK);
• b. providing a second polypeptide comprising the amino acid sequence of SEQ ID NO:
• 1, said second polypeptide is conjugated to a second protein, wherein the second protein is in proximity to the receptor and is selected from the group consisting of GAP43, KRas, HRas and CD8, wherein the second polypeptide is capable of interacting with the first polypeptide to form a modified Oplophorus luciferase to produce a luminescent signal when a test compound binds the receptor and the first protein moves to the receptor in proximity of the second protein;
• c. contacting a test agent with the receptor;
• d. adding a substrate for Oplophorus luciferase;
• and
• e. detecting a luminescent signal, thereby identifying an agonist or an antagonist of the receptor.