Cell biology: The proteasome assembly line

Abstract

The assembly of the proteasome — the cellular machine that eliminates unwanted proteins — is a carefully choreographed affair, involving a complex sequence of steps overseen by dedicated protein chaperones.

Figure 1. A model of proteasome regulatory-particle assembly^,

a, ‘Templating’ Rpt4 and Rpt6 proteins (orange) bind the Rpn14 chaperone and connect to the core particle. Rpn14 and the core particle α-subunit compete for binding to the carboxy-terminal domain of Rpt, and the chaperone is displaced following Rpt–α-subunit interaction. b, The non-ATPase subunit Rpn2 might stabilize this complex, termed BP2–CP. c, Other Rpt ATPases (red) are transferred to the core particle by chaperones Hsm3 and Nas6. Hsm3 is found in the intermediate complex BP1, which also contains Rpt1, 2 and 5 and Rpn1. The specific interactions among these proteins and their order of addition to the emerging Rpt ring are not known. For clarity, Rpn1 and Rpn2 are not shown on the core particle. d, Completion of the ATPase ring fully activates the proteasome. Formation of the base–core-particle complex is presumably followed by assembly of the intact proteasome. The interaction between the base and the lid is predicted to require Rpn10. Only one regulatory particle is shown.