Proteasoms

Proteasomes are large protease complexes that degrade unwanted or damaged proteins in eukaryotic cells as part of the ubiquitin-proteasome system (UPS). They play a central role in protein turnover, regulation of the cell cycle, and stress responses, and contribute to antigen processing for MHC class I presentation.

The core particle, called the 20S proteasome, is a cylindrical complex formed by four stacked rings: two outer rings of seven alpha subunits and two inner rings of seven beta subunits. The beta subunits harbor the proteolytic active sites and include beta1 (caspase-like), beta2 (trypsin-like), and beta5 (chymotrypsin-like) activities. In eukaryotes, the 20S core associates with one or two 19S regulatory particles to form the 26S proteasome, which recognizes polyubiquitinated substrates, unfolds them, and translocates them into the core for degradation. Alternative activators such as PA28 (11S) or PA200 can cap the core and regulate antigen processing and other pathways.

The 26S proteasome is essential for controlled proteolysis of regulatory proteins, removal of misfolded proteins, and generation of peptide fragments for the immune system. Proteasomes are present in the cytosol and nucleus in most cells, with additional roles in certain organelles. In the immune system, immunoproteasomes replace standard catalytic subunits under inflammatory conditions to optimize antigen presentation.

Proteasome activity can be inhibited by drugs like bortezomib and carfilzomib, which are used in treating multiple myeloma. Dysregulation of proteasome function has been implicated in aging and neurodegenerative diseases.