SCF ubiquitin ligase complex

Definition

Target type: cellularcomponent

A ubiquitin ligase complex in which a cullin from the Cul1 subfamily and a RING domain protein form the catalytic core; substrate specificity is conferred by a Skp1 adaptor and an F-box protein. SCF complexes are involved in targeting proteins for degradation by the proteasome. The best characterized complexes are those from yeast and mammals (with core subunits named Cdc53/Cul1, Rbx1/Hrt1/Roc1). [PMID:15571813, PMID:15688063]

The SCF (Skp1-Cullin-F-box) ubiquitin ligase complex is a multi-protein complex that plays a critical role in the ubiquitination of target proteins, leading to their degradation by the proteasome. This complex is highly modular, allowing it to target a wide range of proteins involved in diverse cellular processes. The core structure of the SCF complex comprises four main components:

* **Skp1 (S-phase kinase-associated protein 1):** This protein acts as a scaffold, bridging the F-box protein to the Cullin-RING ligase (CRL) complex.
* **Cullin 1 (CUL1):** This protein serves as a scaffold, binding to both Skp1 and the RING domain protein RBX1.
* **RBX1 (RING-box protein 1):** This protein contains a RING domain, a specialized protein domain that facilitates the transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to the target protein.
* **F-box protein:** This protein is the substrate recognition subunit. It binds to specific target proteins through its F-box motif and recruits them to the SCF complex. The F-box protein family is diverse, allowing SCF complexes to target a wide range of proteins.

The SCF complex assembles through a series of interactions. The F-box protein binds to Skp1, which then interacts with Cullin 1. Cullin 1 further binds to RBX1. This assembled complex then interacts with a ubiquitin-conjugating enzyme (E2) and the target protein.

The mechanism of ubiquitination by SCF involves several steps:

1. **Target protein binding:** The F-box protein binds to the target protein, typically through a specific recognition motif.
2. **Ubiquitin transfer:** The E2 enzyme, loaded with ubiquitin, interacts with RBX1. The RING domain of RBX1 facilitates the transfer of ubiquitin from E2 to the target protein.
3. **Polyubiquitination:** The initial ubiquitin molecule on the target protein serves as a signal for further ubiquitination events. Multiple ubiquitin molecules are then attached to the target protein in a chain, forming a polyubiquitin chain.
4. **Proteasomal degradation:** The polyubiquitinated target protein is recognized by the proteasome, a large protein complex that degrades the protein into short peptides.

The SCF complex is essential for the regulation of various cellular processes, including cell cycle progression, DNA replication, signal transduction, and protein quality control. Dysregulation of SCF activity can lead to various diseases, including cancer and neurodegenerative disorders.

In summary, the SCF complex is a highly versatile and essential ubiquitin ligase that plays a central role in regulating protein degradation, thus influencing a wide range of cellular functions.'
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Proteins (3)

Compounds (5)