cullin family protein binding

Definition

Target type: molecularfunction

Binding to a member of the cullin family, hydrophobic proteins that act as scaffolds for ubiquitin ligases (E3). [GOC:ha, InterPro:IPR016158, PMID:18698375]

Cullin family proteins are a group of scaffold proteins that play crucial roles in the ubiquitin proteasome system (UPS), a major cellular pathway responsible for protein degradation. Cullin proteins act as central hubs in multi-protein complexes known as cullin-RING ubiquitin ligases (CRLs), which specifically target proteins for ubiquitination, a process that marks them for degradation by the proteasome. The molecular function of cullin family protein binding involves the following key steps:

1. **Scaffold Formation:** Cullin proteins act as scaffolds, providing a framework for the assembly of CRL complexes. They possess a conserved structure, typically consisting of seven domains, each with distinct functional roles. The C-terminal domain of cullin proteins interacts with RING-box proteins, which are responsible for recruiting E2 ubiquitin-conjugating enzymes. The N-terminal domain binds to substrate-recognition subunits called adaptor proteins, which are specific for distinct target proteins.

2. **Substrate Recognition and Targeting:** Adaptor proteins, also known as substrate receptor proteins, bind to specific target proteins through various mechanisms, including protein-protein interactions, post-translational modifications, and/or recognition of specific motifs or domains within the target protein. This recognition event is crucial for ensuring the specificity of the CRL complex towards its intended substrate.

3. **Ubiquitin Transfer:** Upon substrate recognition, the E2 ubiquitin-conjugating enzyme, bound to the RING domain of the CRL, transfers ubiquitin molecules from a donor protein (E1 ubiquitin activating enzyme) to the target protein. This process involves a series of enzymatic reactions, where ubiquitin is first activated by E1 and then transferred to the E2 enzyme. The E2-ubiquitin conjugate then interacts with the RING domain of the CRL, facilitating the transfer of ubiquitin to the target protein.

4. **Ubiquitin Chain Formation:** The initial ubiquitin molecule attached to the target protein serves as a signal for the addition of further ubiquitin molecules, resulting in the formation of a polyubiquitin chain. The specific linkage of ubiquitin molecules within the chain (e.g., Lys48 or Lys63 linkage) determines the fate of the target protein. Lys48-linked chains typically target proteins for proteasomal degradation, whereas Lys63-linked chains are often involved in other cellular processes, such as DNA repair and signal transduction.

5. **Proteasomal Degradation:** Once a target protein is sufficiently ubiquitinated, it is recognized by the proteasome, a large protein complex responsible for protein degradation. The proteasome unfolds and degrades the ubiquitinated protein into short peptides, which can be further processed and recycled by the cell.

In summary, cullin family protein binding facilitates the assembly of CRL complexes, which specifically target proteins for ubiquitination and subsequent degradation by the proteasome. This process plays a crucial role in regulating various cellular processes, including cell cycle control, signal transduction, DNA repair, and immune response.'
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Proteins (2)

Compounds (7)