GTPase

A GTPase (Guanosine triphosphatase) is a hydrolase enzyme that binds to guanosine triphosphate (GTP) and hydrolyzes it to guanosine diphosphate (GDP) and inorganic phosphate. This hydrolysis is a critical energy-releasing process that drives a variety of cellular functions. GTPases act as molecular switches, cycling between an active, GTP-bound form and an inactive, GDP-bound form.

The activity of GTPases is tightly regulated by two main classes of regulatory proteins:

• Guanine nucleotide exchange factors (GEFs): GEFs stimulate the release of GDP, allowing GTP to bind in its place, thus activating the GTPase. GTP is usually much more abundant than GDP in the cell, ensuring GTP binding once GDP is released.

• GTPase-activating proteins (GAPs): GAPs enhance the intrinsic GTP hydrolysis rate of the GTPase, accelerating the inactivation of the protein by converting GTP to GDP.

The balance between GEF and GAP activity determines the proportion of GTPase in the active (GTP-bound) and inactive (GDP-bound) states, and thus, the activity of downstream signaling pathways.

GTPases are involved in a wide range of cellular processes, including:

• Signal transduction: Many signaling pathways rely on GTPases to transmit signals from cell surface receptors to intracellular targets. Examples include Ras superfamily GTPases.
• Protein synthesis: Elongation factors involved in translation are GTPases.
• Vesicular trafficking: GTPases regulate the formation, transport, and fusion of vesicles within the cell. Examples include Rab GTPases.
• Nuclear transport: Ran GTPase plays a crucial role in regulating the movement of molecules between the nucleus and the cytoplasm.
• Cell growth and differentiation: Some GTPases are involved in controlling cell proliferation, differentiation, and apoptosis.
• Cytoskeletal organization: Rho family GTPases are key regulators of actin cytoskeleton dynamics, influencing cell shape, motility, and adhesion.

Dysregulation of GTPase activity is implicated in various diseases, including cancer, developmental disorders, and infectious diseases. Mutations that constitutively activate GTPases, or disrupt their regulation, can lead to uncontrolled cell growth and tumorigenesis.