GTPases en hun regelgevingregulatie

Guanosine triphosphate, GTP, a close relative of ATP, is a small molecule important for the regulation of protein function.  

G-proteins are proteins regulated by GTP binding. These proteins have intrinsic GTPase activity, that is when GTP is bound, they can catalyze its hydrolysis to guanosine diphosphate, GDP.  

G-proteins are divided into two categories, small and large. The small, or monomeric, G-proteins are a single protein subunit that is activated by various intracellular signaling pathways.

In contrast, the large, or heterotrimeric, G-proteins contain three subunits and are activated by membrane-bound G-protein coupled receptors. 

GTPases act as a molecular switch, where the GDP bound state usually is inactive while the GTP bound state is active. GTP binding followed by GTP to GDP hydrolysis is part of the GDP/GTP cycle.

The cycle starts when a guanine exchange factor, GEF, induces a conformational change in the G-protein that causes the release of GDP.  

GTP quickly binds to the now-empty nucleotide-binding site as GTP is abundant in the cytoplasm. The G-protein is now switched into its active state with GTP bound.  

G-proteins have intrinsic GTPase activity to hydrolyze the bound molecule; however, the GTP breakdown by the enzyme is a slow process without additional cellular signals.

Therefore, when it is time for the G-protein to be switched off, a GTPase activating protein, or GAP, will bind and enhance the GTPase activity of the protein. The GTP is broken down into GDP and inorganic phosphate and the G-protein returns to its inactive state completing the cycle.