RabGGTase

Rab geranylgeranyltransferase, also known as RabGGTase or GGTase II, is a eukaryotic prenyltransferase that modifies Rab GTPases by attaching geranylgeranyl groups to their C-terminal cysteine residues. This lipid modification increases Rab proteins’ hydrophobicity, enabling their association with membranes and their participation in vesicular trafficking.

Biochemical composition: In many eukaryotes, RabGGTase is a heterodimer consisting of a catalytic alpha subunit and a beta subunit. The enzyme works together with Rab escort protein (REP1 or REP2), which binds Rab GTPases in the cytosol and delivers them to RabGGTase for prenylation.

Substrate and chemistry: The substrates are Rab GTPases that display C-terminal CC or CXC motifs. The donor is geranylgeranyl pyrophosphate (GGPP). RabGGTase catalyzes the transfer of one or two geranylgeranyl groups to the Rab cysteines, producing a doubly geranylgeranylated Rab that can associate with membranes.

Biological role: Prenylated Rab proteins participate in the regulation of vesicle formation, transport, tethering, and fusion between organelles such as endosomes, the Golgi apparatus, and the plasma membrane. RabGGTase activity is essential for correct Rab localization and function, which in turn supports proper intracellular trafficking and organelle homeostasis.

Clinical and research notes: Disruptions in Rab prenylation, REP function, or RabGGTase components can impair trafficking and have been linked to disease processes in research contexts. RabGGTase is also a target for pharmacological inhibitors used to study Rab-dependent trafficking pathways.