Ubiquitin-mediated proteolytic pathway

Most of the proteins that are degraded in the cytosol are delivered to large protein complexes called proteasomes, which are present in many copies and are dispersed throughout the cell.

Each 26S proteasome consists of a central cylinder formed from multiple distinct proteases, whose active sites are thought to face an inner chamber.

Each end of the cylinder is "stoppered" by a large protein complex formed from at least 10 types of polypeptides, some of which hydrolyze ATP.

These protein stoppers are thought to select the proteins for destruction by binding to them and feeding them into the inner chamber of the cylinder, where multiple proteases degrade the proteins to short peptides that are then released.

A conjugating enzyme catalyzes formation of a peptide bond between ubiquitin (Ub) and the side-chain –NH₂ of a lysine residue in a target protein.

Additional Ub molecules are added, forming a multi-ubiquitin chain.