Plasticity in the structure and assembly of proteasomes.

Proteasomes are large multisubunit protease complexes found in all domains of life, where they execute regulatory and quality control degradation critical for organismal health. The canonical form of the proteasome, known as the 26S proteasome, consists of a 28-subunit barrel-shaped proteolytic core particle (CP) that is capped on its barrel ends by the 19-subunit regulatory particle (RP). The RP recognizes and captures substrates destined for degradation, mechanically unfolds them using energy derived from ATP, and translocates them through a gated pore at the surface of the CP into the proteolytic sites housed in its hollow center. Due to their exceptional size and subunit complexity, biogenesis of 26S proteasomes is a highly orchestrated process facilitated by dedicated assembly chaperones and conserved features of its subunits. Since the initial discovery of canonical 26S proteasomes, numerous noncanonical CPs harboring distinct subunit compositions have been detected, as have several alternative non-RP regulators of CP function. Here, we review the structure and assembly of canonical and noncanonical forms of the proteasome and highlight recent structural studies that have greatly clarified our understanding of how these fascinating and complicated molecular machines form rapidly and faithfully in the cellular milieu. In addition, we explore the assembly mechanisms that yield plasticity in the subunit composition of proteasomes, as well as emerging evidence of plasticity in the assembly pathways by which proteasomes are built in cells.