Proteosome

Proteasome

The proteasome is a complex and essential protein structure found within all eukaryotic cells, as well as in some prokaryotes and archaea. It plays a critical role in maintaining cellular homeostasis by degrading unneeded or damaged proteins through a process known as proteolysis. This process is vital for regulating the concentration of specific proteins and thus maintaining the balance of cellular processes.

Structure

The proteasome is a large, multi-subunit complex that is typically composed of a core particle (CP) and one or two regulatory particles (RPs). The core particle, also known as the 20S proteasome, is a barrel-shaped structure made up of four stacked rings, each containing seven protein subunits. The two outer rings are composed of alpha subunits, while the two inner rings are composed of beta subunits, which contain the proteolytic active sites.

The regulatory particles, often referred to as the 19S regulatory particles, cap one or both ends of the core particle. These RPs are responsible for recognizing ubiquitin-tagged proteins, unfolding them, and translocating them into the core particle for degradation.

Function

The primary function of the proteasome is to degrade proteins that have been tagged for destruction by a small protein called ubiquitin. This tagging process is known as ubiquitination and involves a cascade of enzymatic reactions that attach ubiquitin molecules to lysine residues on the target protein. Once a protein is polyubiquitinated, it is recognized by the 19S regulatory particle of the proteasome.

Upon recognition, the regulatory particle unfolds the protein and translocates it into the core particle, where it is degraded into small peptides. These peptides are then released into the cytosol, where they can be further degraded into amino acids or used for antigen presentation by the immune system.

Biological Importance

The proteasome is crucial for numerous cellular processes, including:

• Cell Cycle Regulation: By degrading cyclins and other regulatory proteins, the proteasome helps control the progression of the cell cycle.
• Apoptosis: The degradation of pro-apoptotic and anti-apoptotic factors by the proteasome can influence cell death pathways.
• DNA Repair: The proteasome regulates the levels of proteins involved in DNA repair, thus maintaining genomic stability.
• Immune Response: The proteasome generates peptides that are presented on MHC class I molecules, which are essential for the immune system to recognize and destroy infected or cancerous cells.

Clinical Significance

Dysfunction of the proteasome system is implicated in various diseases, including cancer, neurodegenerative disorders such as Parkinson's and Alzheimer's disease, and autoimmune diseases. Proteasome inhibitors, such as bortezomib, are used as therapeutic agents in the treatment of multiple myeloma and certain types of lymphoma.

Also see

• Ubiquitin
• Protein Degradation
• Cell Cycle
• Apoptosis
• DNA Repair
• Immune System