GTPTubulin

GTP-tubulin refers to tubulin dimers bound to guanosine triphosphate (GTP). In eukaryotic tubulins, the α/β tubulin heterodimer carries two GTP molecules: one bound to α-tubulin, which is non-exchangeable and remains bound for the lifetime of the dimer, and one bound to β-tubulin, which is exchangeable and hydrolyzable after incorporation into microtubules.

During microtubule assembly, GTP-tubulin dimers add to the growing plus end of a microtubule in their GTP-bound form. After incorporation, the GTP bound to β-tubulin is hydrolyzed to GDP, while the α-bound GTP remains. This hydrolysis alters intersubunit interactions and lowers lattice stability, making GDP-tubulin within the microtubule more prone to disassembly if not replenished by new GTP-tubulin.

A key concept linked to GTP-tubulin is the GTP cap: a region at the growing end enriched in GTP- or GDP-Pi-bound tubulin that stabilizes the microtubule and suppresses catastrophe. When the rate of GTP hydrolysis catches up with or surpasses subunit addition, the cap is lost and rapid depolymerization can occur. Microtubule-associated proteins and pharmacological agents modulate hydrolysis rates and cap stability, thereby tuning dynamic behavior.

GTP-tubulin dynamics underlie essential cellular processes, including mitosis, intracellular transport, and maintenance of cell shape. They are a central focus of structural biology and pharmacology, with implications for understanding microtubule function and developing therapeutics targeting tubulin dynamics.