GDPtoGTP

GDPtoGTP refers to the nucleotide exchange step by which guanine nucleotide–binding proteins switch from a GDP-bound, inactive state to a GTP-bound, active state. The term is not a separate molecule but a descriptor of the regulatory process that governs the activity cycle of G proteins, including small GTPases and heterotrimeric G proteins.

In most systems, the exchange is catalyzed by guanine nucleotide exchange factors (GEFs). GEFs bind to the GDP-bound protein, destabilizing the GDP interaction and promoting its release. After GDP dissociates, intracellular GTP readily binds due to its higher cellular concentration, converting the protein to the active form. The active GTP-bound protein then carries out its signaling or trafficking functions until intrinsic GTPase activity, often accelerated by GTPase-activating proteins (GAPs), hydrolyzes GTP back to GDP, returning the protein to its inactive state.

This mechanism is central to diverse cellular processes, including signal transduction, vesicle trafficking, and cytoskeletal dynamics. Families involved include Ras-like small GTPases (such as Ras, Rho, and Rab proteins) and heterotrimeric G proteins (Gs, Gi/o, Gq/11 families). Examples of regulatory interactions include SOS acting as a GEF for Ras and Rabex-5 for Rab proteins.

Dysregulation of GDPtoGTP exchange—through mutations in GTPases, GEFs, or GAPs—can lead to abnormal signaling and disease, notably cancer and developmental disorders. Understanding this exchange step remains essential for insights into cellular control and potential therapeutic targeting.