GTPase

GTPase is an enzyme that hydrolyzes guanosine triphosphate (GTP) to guanosine diphosphate (GDP) and inorganic phosphate. In cells, many GTPases act as molecular switches that cycle between an active GTP-bound state and an inactive GDP-bound state, regulating processes such as signal transduction, cytoskeletal organization, and membrane trafficking.

Two broad classes exist: small GTPases (~20–25 kDa) and large GTPases. Small GTPases include members of the Ras superfamily such as Ras, Rab, Rho, Rac, Cdc42, Arf, and Ran. Large GTPases include dynamin and other members involved in organelle dynamics and vesicle scission. Some translation factors, such as EF-Tu, are also GTPases.

GTPases belong to the P-loop NTPase family and harbor conserved motifs such as the G1/P-loop, G3(DxxG), G4(NKXD), and G5 elements. They switch between conformations of switch I and II depending on nucleotide state, governing effector interactions. Intrinsic hydrolysis is slow and accelerated by GTPase-activating proteins (GAPs); GDP release and exchange for GTP are promoted by guanine nucleotide exchange factors (GEFs). In many small GTPases, GDP dissociation inhibitors (GDIs) regulate membrane localization by controlling exposure of lipid-modified C-termini.

Biological roles include signaling cascades such as the Ras-MAPK pathway, vesicle trafficking (Rab family), and cytoskeletal dynamics (Rho, Rac, Cdc42). They act as rapid on/off switches on timescales of seconds to minutes. Misregulation can contribute to disease; most notably, Ras mutations are common in cancer. Bacteria also employ GTPases in protein synthesis and ribosome function (for example EF-Tu and EF-G) and in signaling.