<P> When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a guanine nucleotide exchange factor (GEF). The GPCR can then activate an associated G protein by exchanging the GDP bound to the G protein for a GTP . The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (G, G, G, G). </P> <P> The 2012 Nobel Prize in Chemistry was awarded to Brian Kobilka and Robert Lefkowitz for their work that was "crucial for understanding how G protein--coupled receptors function". There have been at least seven other Nobel Prizes awarded for some aspect of G protein--mediated signaling . As of 2012, two of the top ten global best - selling drugs (Advair Diskus and Abilify) act by targeting G protein--coupled receptors . </P> <P> The exact size of the GPCR superfamily is unknown, but nearly 800 different human genes (or ~ 4% of the entire protein - coding genome) have been predicted to code for them from genome sequence analysis . Although numerous classification schemes have been proposed, the superfamily was classically divided into three main classes (A, B and C) with no detectable shared sequence homology between classes . </P> <P> The largest class by far is class A, which accounts for nearly 85% of the GPCR genes . Of class A GPCRs, over half of these are predicted to encode olfactory receptors, while the remaining receptors are liganded by known endogenous compounds or are classified as orphan receptors . Despite the lack of sequence homology between classes, all GPCRs have a common structure and mechanism of signal transduction . The very large rhodopsin A group has been further subdivided into 19 subgroups (A1 - A19). </P>

How does a g protein coupled receptor work