GTPaasit

GTPases are a broad family of enzymes that bind guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). In their GTP-bound state they are typically active and act as molecular switches that regulate a variety of cellular processes, while conversion to GDP-bound form often halts signaling or activity. Activation and inactivation are tightly controlled by regulatory proteins: guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP, GTPase-activating proteins (GAPs) accelerate GTP hydrolysis, and, for many small GTPases, guanine nucleotide dissociation inhibitors (GDIs) modulate localization and nucleotide exchange.

Most GTPases belong to the P-loop NTPase superfamily and share a conserved GTPase domain, with switch regions that change conformation depending on whether GTP or GDP is bound. These conformational changes determine interactions with downstream effectors, regulators, and membranes. Many small GTPases are anchored to membranes through lipid modifications such as prenylation or palmitoylation, which helps coordinate signaling with subcellular location.

Two major classes are recognized: small GTPases of the Ras superfamily (including Ras, Rho, Rab, Arf and Ran) and larger GTPases such as dynamin and translation factors like EF-Tu. Within cells, Ras family members regulate growth factor signaling; Rho family proteins control cytoskeletal dynamics; Rab proteins govern vesicle trafficking; Ran mediates nucleocytoplasmic transport; Arf proteins participate in vesicle formation and trafficking.

Dysregulation of GTPases is linked to diseases including cancer (notably Ras mutations) and developmental disorders. Therapeutic approaches target regulators, post-translational modifications, or specific mutant forms to modulate GTPase activity.