Highlights The oncogenic Gαs mutation R201C allows GDP-bound Gαs to activate adenylyl cyclase GDP-bound Gαs(R201C/C237S) adopts an active state in its crystal structure The R201C mutation activates Gαs by stabilizing an intramolecular H-bond network Loss-of-function mutations R228C and R265H destabilize the GTP active state of Gαs A few days ago, researchers from Howard Houston Medical School discovered a novel protein mutation in pituitary tumors, which may subvert the traditional concept,…