geranylgeranyltransferase

Geranylgeranyltransferase is a family of enzymes that catalyzes the transfer of a geranylgeranyl lipid group from geranylgeranyl pyrophosphate (GGPP) to specific cysteine residues on target proteins. This post-translational modification, known as geranylgeranylation, provides a hydrophobic anchor that promotes association of the modified proteins with cellular membranes and influences their localization and function.

There are two main forms in humans: geranylgeranyltransferase I (GGTase I) and geranylgeranyltransferase II (GGTase II). GGTase I is a heterodimer that transfers a single geranylgeranyl group to cysteine within a CaaX motif at the C-terminus of a subset of proteins, including several members of the Rho family of small GTPases and other CAAX-containing proteins. The modification facilitates membrane attachment and proper signaling or trafficking.

GGTase II, also known as Rab geranylgeranyltransferase, is a heterodimer that requires the Rab escort protein (REP) to deliver Rab GTPase substrates. GGTase II recognizes Rab proteins that terminate in CC or CXC motifs and adds one or two geranylgeranyl groups, enabling Rab localization to membranes and participation in vesicular trafficking and endomembrane system function.

Biological significance and clinical relevance center on the essential role of geranylgeranylation in membrane targeting of small GTPases and Rab proteins. Disruption of GGTase activity can impair trafficking, signaling, and cytoskeletal dynamics, and has been explored as a potential target in cancer and infectious disease research through the use of specific inhibitors.