Heterotrimeric G Protein Cycle

Abstract

This teaching resource provides two types of insight into the heterotrimeric G protein cycle. The interactive animation shows the basic heterotrimeric G protein cycle and allows the user to then add three different regulators of the cycle, an RGS (regulator of G protein signaling) protein, a GDI (guanine nucleotide dissociation inhibitor) protein, or a guanine nucleotide exchange factor (GEF). G proteins are comprised of two subunits, α and an obligate dimer βγ. The structure movie shows an computer-generated interpretation of the conformational changes in the α subunit that are associated with GTP binding and hydrolysis. The basic G protein cycle consists of a G protein-coupled receptor (GPCR) activating the G protein by promoting the exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP), which allows the α and βγ subunits to separate and activate downstream targets. The signal is terminated when the α subunit hydrolyzes GTP and the α and βγ subunits reassociate. The animation allows the user to choose to play the cycle with or without additional regulators and see the effect on the signaling duration. RGS stimulates the GTPase activity of the α subunit and terminates signaling faster. GDI prevents the dissociation of GDP from the α subunit and blocks reassociation of the βγ subunit, thus extending βγ signaling. GEF enhances the rate of GTP loading in the presence of an activated receptor thus accelerating the speed of the response.