GTPasas

GTPases (also known as GTPasas in some languages) are enzymes that hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). They function as molecular switches in many cellular processes, cycling between active GTP-bound and inactive GDP-bound states. Their activity is controlled by regulatory proteins that promote nucleotide exchange and GTP hydrolysis, enabling them to relay signals in growth, trafficking, cytoskeleton, and nuclear transport.

Most GTPases belong to the small GTPase family, collectively known as the Ras superfamily, including Ras, Rho, Rab, Ran, and Arf subfamilies. These proteins participate in diverse tasks: Ras in cell proliferation; Rab in vesicle trafficking; Rho in cytoskeleton dynamics; Ran in nucleocytoplasmic transport; Arf in vesicle formation and lipid modification.

Structurally, GTPases are P-loop NTPases with conserved nucleotide-binding motifs. In the GTP-bound form they adopt conformations that engage effectors; hydrolysis to GDP switches those conformations. Activation and inactivation are typically regulated by accessory factors rather than intrinsic rates alone.

Regulation involves guanine nucleotide exchange factors (GEFs), which promote GDP release and GTP binding, and GTPase-activating proteins (GAPs), which accelerate hydrolysis. Guanine nucleotide dissociation inhibitors (GDIs) regulate cycling and localization for several GTPases, especially Rab proteins, by masking membrane anchors. Lipid modifications like prenylation or myristoylation also aid membrane association.

Dysregulation of GTPases is linked to disease. Oncogenic Ras mutations contribute to cancers; other GTPases participate in developmental disorders and host-pathogen interactions. Because of their central signaling role, GTPases are frequent subjects of biochemical and structural studies and of efforts to develop targeted therapies.