The Functional Cycle of Heterotrimeric G Proteins

Signal transmission via G-proteins takes place in close association with the iimer side of the cell membrane. Both the a-subunit and the Pycomplex are associated with the membrane via membrane anchors (see 5.5.8). 

Like all regulatory GTPases, the heterotrimeric G-proteins nm through a cyclical transition between an inactive, GDP-boimd form and an active, GTP-boimd form. Fig. 5.16 sketches the different functional states and the role of the individual subunits. 

In the inactive groimd state, the G-proteins exist as Ga - GDP - (PY)-heterotrimers. The receptor is not occupied by the hormone the sequential effector molecule is inactive. 

GTP binding has two consequences firstly, the Pycomplex dissociates and secondly, the binding to the activated receptor is cancelled. The free a-subunit with bound GTP represents the activated G GTP form of the G-protein and transmits the signal further. The receptor released from the complex can activate other G-proteins, enabling amplification of the signal. For a detailed model of Ga activation see liri et al., (1998). 

The interaction of G GTP with the corresponding effector molecule leads to inactivation of the former and thus to initiation of the next step in the signal transmission chain. The Pycomplex released during activation can also perform a signal-mediating function (see 5.5.7). 

By catalyzing the expulsion of the bound GDP from the Ga GDP (fly) complex, the activated receptor functions as a nucleotide exchange factor, GEF. It is the agonist- 

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