“…The G protein signaling cycle is regulated by several proteins, including GEFs (e.g., GPCRs, GIV/Girdin, or Ric-8A) and GTPase-activating proteins [GAPs; e.g., regulators of G protein signaling (RGS)]. 48 , 49 , 50 , 51 , 52 As our data support slow AHD closing enabled by the long-lived intermediate state of Gαs after GTPγS binding, we searched for an AHD-binding protein that might regulate the AHD closing kinetics. To this end, we employed Y2H library screening with the Gαs AHD as bait and identified melanoma-associated antigen D2 (MAGE D2, NM_014599) as a novel Gαs AHD-binding protein ( Figure S8 A).…”