CAAX-protein geranylgeranyltransferase complex

Definition

Target type: cellularcomponent

A heterodimeric enzyme, composed of an alpha and a beta subunit. Participates in the post-translational C-terminal modification of several small GTPases, allowing their targeting to the membrane. [PMID:9781874]

The CAAX-protein geranylgeranyltransferase complex is a multi-subunit enzyme responsible for the post-translational modification of proteins with a CAAX motif, where C is cysteine, A is an aliphatic amino acid, and X is any amino acid. This modification involves the attachment of a geranylgeranyl group, a 20-carbon isoprenoid, to the cysteine residue at the carboxyl terminus of the protein. This process is essential for the proper localization, function, and signaling of a variety of proteins, including those involved in cell growth, differentiation, and membrane trafficking.

The complex is composed of two major subunits:

1. **Rab escort protein (REP):** This protein interacts with the CAAX motif and facilitates the transfer of the geranylgeranyl group from the prenyltransferase to the target protein.
2. **Geranylgeranyltransferase I (GGTase I):** This is the catalytic subunit of the complex and directly catalyzes the transfer of the geranylgeranyl group to the cysteine residue. GGTase I is a heterodimer composed of α and β subunits.

The geranylgeranyltransferase complex is localized to the endoplasmic reticulum (ER) membrane, where it interacts with various proteins that contain CAAX motifs. Once the geranylgeranyl group is attached, the prenylated protein can then be further modified by other enzymes, such as proteases, which remove the three terminal amino acids (AAX) of the CAAX motif.

The complex functions in a step-wise manner:

1. The CAAX-containing protein interacts with REP.
2. The complex then binds to GGTase I, which transfers the geranylgeranyl group to the cysteine residue of the CAAX motif.
3. The prenylated protein dissociates from the complex.

This process is highly regulated and is influenced by factors such as the availability of substrates, the activity of regulatory proteins, and the cellular environment.

In addition to its essential role in protein modification, the geranylgeranyltransferase complex is also implicated in various cellular processes and diseases. For example, mutations in GGTase I have been linked to various diseases, such as retinitis pigmentosa and Alzheimer's disease. Furthermore, the complex has been shown to be involved in the pathogenesis of certain cancers, suggesting its potential as a therapeutic target.

Overall, the CAAX-protein geranylgeranyltransferase complex plays a critical role in the post-translational modification of proteins and is essential for the proper function of a wide range of cellular processes. Its involvement in various diseases underscores its importance as a potential target for drug development.'
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Proteins (4)

Compounds (31)