Rab geranylgeranyltransferase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: 2 geranylgeranyl diphosphate + protein-cysteine = 2 S-geranylgeranyl-protein + 2 diphosphate. This reaction is the formation of two thioether linkages between the C-1 atom of the geranylgeranyl groups and two cysteine residues within the terminal sequence motifs XXCC, XCXC or CCXX. Known substrates include Ras-related GTPases of a single family and the Rab family. [EC:2.5.1.60, GOC:mah, PMID:8621375]

Rab geranylgeranyltransferase (RabGGTase) is an enzyme that catalyzes the transfer of two geranylgeranyl groups from geranylgeranyl pyrophosphate (GGPP) to the cysteine residues at the C-terminal CAAX motif of Rab GTPases. Rab GTPases are small GTP-binding proteins that play crucial roles in intracellular membrane trafficking and vesicle transport. They act as molecular switches, cycling between an active GTP-bound and an inactive GDP-bound state, and their localization and activity are tightly regulated by various factors, including prenylation.

RabGGTase is a heterodimer consisting of two subunits: Rab escort protein (REP) and Rab geranylgeranyl transferase alpha (GGTase-alpha). REP is responsible for binding and delivering Rab GTPases to GGTase-alpha, while GGTase-alpha performs the actual geranylgeranylation reaction.

The process of Rab geranylgeranylation occurs in several steps:

1. **Binding of Rab GTPase to REP:** The Rab GTPase binds to REP in its GDP-bound state, forming a complex.
2. **Delivery to GGTase-alpha:** The Rab-REP complex interacts with GGTase-alpha, facilitating the transfer of the Rab GTPase to the active site of the enzyme.
3. **Prenylation:** GGTase-alpha catalyzes the transfer of two geranylgeranyl groups from GGPP to the cysteine residues at the C-terminal CAAX motif of the Rab GTPase.
4. **Release of Rab GTPase:** The prenylated Rab GTPase dissociates from GGTase-alpha and REP, and it is ready to participate in membrane trafficking.

Geranylgeranylation plays a crucial role in the function of Rab GTPases by:

* **Membrane association:** Prenylation anchors Rab GTPases to cellular membranes, enabling their localization to specific organelles and compartments.
* **Protein-protein interactions:** The prenyl groups on Rab GTPases mediate interactions with other membrane-associated proteins, such as effectors and tethering factors, facilitating the formation of functional complexes.
* **Regulation of activity:** Prenylation can influence the GTPase activity of Rab proteins, affecting their ability to bind to GTP and activate downstream signaling pathways.

In summary, Rab geranylgeranyltransferase activity is essential for the proper function of Rab GTPases, ensuring their correct localization, interaction with other proteins, and regulation of their activity. This enzymatic activity is crucial for maintaining cellular membrane trafficking and vesicle transport, which are fundamental processes in various cellular functions, including cell signaling, nutrient transport, and organelle biogenesis.'
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Proteins (3)

Compounds (31)