proteasomaler

The proteasome is a large, multicatalytic protease complex found in all eukaryotic cells and some bacteria, playing a crucial role in protein degradation and the regulation of various cellular processes. It is responsible for breaking down damaged, misfolded, or unnecessary proteins into small peptides, which are then further processed by other enzymes or recycled into amino acids. The proteasome is essential for maintaining cellular homeostasis, immune responses, and cell cycle regulation.

Proteasomes are composed of a 20S core particle (CP) and, in most eukaryotic cells, two 19S regulatory particles (RPs) that cap each end of the CP, forming the 26S proteasome. The 20S CP is a barrel-shaped structure made up of four stacked rings, each containing seven subunits. The inner two rings are composed of catalytic β-subunits that cleave peptide bonds, while the outer rings consist of non-catalytic α-subunits that regulate substrate entry. The 19S RP recognizes ubiquitinated proteins, unfolds them, and threads them into the 20S CP for degradation.

Ubiquitination is a key process in proteasomal degradation, where ubiquitin molecules are covalently attached to target proteins by a series of enzymes (E1, E2, and E3). This tag marks proteins for recognition and degradation by the proteasome. The proteasome also plays a role in antigen presentation by breaking down proteins into peptides that can be loaded onto major histocompatibility complex (MHC) class I molecules, which are crucial for the immune system’s ability to recognize and eliminate infected or cancerous cells.

Dysregulation of the proteasome is associated with various diseases, including cancer, neurodegenerative disorders (such as Alzheimer’s and Parkinson’s), and immune deficiencies. Inhibitors of the proteasome, such as bortezomib, are used therapeutically to treat certain types of cancer by disrupting protein degradation pathways in rapidly dividing cells. Research into the proteasome continues to uncover its complex functions and potential as a therapeutic target.