protein farnesyltransferase complex

Definition

Target type: cellularcomponent

A protein complex that possesses protein farnesyltransferase activity. [GOC:mah]

The farnesyltransferase complex is a multi-protein assembly responsible for the post-translational modification of proteins by attaching a farnesyl group, a 15-carbon isoprenoid, to cysteine residues near the C-terminus. This complex is localized to the cytoplasmic side of the endoplasmic reticulum membrane, and it is typically composed of two subunits: **Farnesyltransferase alpha subunit (α-FTase)** and **Farnesyltransferase beta subunit (β-FTase)**.

* **α-FTase:** This subunit is a 46 kDa protein that binds the farnesyl diphosphate (FPP) substrate. It also contains a catalytic site that interacts with the substrate protein.
* **β-FTase:** This subunit is a 48 kDa protein that binds the substrate protein. It also contains a cysteine residue that acts as the nucleophile in the transfer reaction.

The two subunits interact via a complex interface that facilitates the binding of both the protein substrate and the FPP substrate. This interaction is crucial for the proper functioning of the complex.

**Detailed description of the cellular component:**

1. **Localization:** The farnesyltransferase complex is primarily localized to the **cytoplasmic side of the endoplasmic reticulum (ER) membrane**. This localization is essential for the complex to access its protein substrates, which are often synthesized and processed in the ER.
2. **Membrane Association:** While the farnesyltransferase complex is associated with the ER membrane, it is not embedded within the membrane. Rather, it interacts with the membrane through **hydrophobic interactions** between specific amino acid residues within the complex and the lipid bilayer.
3. **Structure:** The complex has a **globular structure** with a well-defined active site that accommodates both the protein substrate and the FPP substrate.
4. **Dynamic Assembly:** The assembly of the α-FTase and β-FTase subunits into the active farnesyltransferase complex is a **dynamic process**. This process can be influenced by factors such as the concentration of substrate proteins and the availability of FPP.

In addition to these core components, other proteins may associate with the farnesyltransferase complex, including:

* **Rab escort protein (REP):** This protein assists in the delivery of Rab proteins to the farnesyltransferase complex.
* **Chaperone proteins:** These proteins can help to prevent misfolding and aggregation of the complex subunits.

**Importance of the Farnesyltransferase Complex:**

The farnesyltransferase complex plays a critical role in various cellular processes, including:

* **Signal transduction:** Farnesylation is essential for the proper function of a wide range of signaling proteins, including Ras GTPases.
* **Cellular trafficking:** Farnesylation of Rab proteins is crucial for their proper targeting and function in vesicle transport.
* **Nuclear localization:** Farnesylation can contribute to the localization of certain proteins to the nucleus.

**Regulation of Farnesyltransferase Activity:**

The activity of the farnesyltransferase complex is tightly regulated, and this regulation is essential for maintaining cellular homeostasis. Factors that influence the activity of the complex include:

* **Substrate availability:** The concentration of protein substrates and FPP can influence the activity of the complex.
* **Post-translational modifications:** The farnesyltransferase complex itself can be subject to post-translational modifications, such as phosphorylation, which can affect its activity.
* **Inhibitors:** Several small-molecule inhibitors have been developed that specifically target the farnesyltransferase complex, and these inhibitors have shown promise as potential therapeutic agents for various diseases.

In conclusion, the farnesyltransferase complex is a complex and dynamic assembly that plays a critical role in various cellular processes. Its localization to the ER membrane, its specific protein-protein interactions, and its tight regulation all contribute to its crucial function in cell signaling, trafficking, and other essential processes.'
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Proteins (4)

Compounds (31)