Liganded Gs-activating GPCR acts as a GEF for Gs

The liganded receptor undergoes a conformational change, generating a signal that is propagated in a manner that is not completely understood to the the G-protein. This stimulates the exchange of GDP for GTP in the G-protein alpha subunit, activating the G-protein.

This event is negatively regulated by some Activators of G protein signaling (AGS) proteins, a class of proteins identified in yeast functional screens for proteins able to activate G protein signaling in the absence of a G protein–coupled receptor (GPCR) (Cismowski et al. 1999, Takesono et al. 1999). AGS proteins contain G protein regulatory (GPR) motifs (also referred to as the GoLoco motif) that bind and stabilize the Galpha subunit in its GDP-bound conformation (Mochizuki et al. 1996, Peterson et al. 2000, Cao et al. 2004, Blumer & Lanier 2014). Some RGS proteins similarly bind to Galpha preventing the exchange of GDP for GTP (Soundararajan et al. 2008).

配体结合的受体发生构象变化，从而产生一种信号，该信号以尚不完全明了的方式传递至G蛋白。这一过程刺激G蛋白α亚基中GDP与GTP的交换，进而激活G蛋白。该事件受到某些G蛋白信号激活剂（AGS）蛋白的负向调控，此类蛋白在酵母功能筛选中得以鉴定，它们能够在没有G蛋白偶联受体（GPCR）的情况下激活G蛋白信号（Cismowski等，1999，Takesono等，1999）。AGS蛋白含有G蛋白调控（GPR）基序（亦称为GoLoco基序），该基序与GDP结合状态的Galpha亚基结合并稳定其结构（Mochizuki等，1996，Peterson等，2000，Cao等，2004，Blumer & Lanier，2014）。一些RGS蛋白同样与Galpha结合，从而阻止GDP与GTP的交换（Soundararajan等，2008）。