Assembly, structure, and function of the 26S proteasome

Abstract

The 26S proteasome is a large multi-protein complex involved in the regulated degradation of ubiquitinated proteins in the cell. The 26S proteasome has been shown to control an increasing number of essential biochemical mechanisms of the cellular lifecycle including DNA synthesis, repair, transcription, translation and cell signal transduction. Concurrently, it is increasingly seen that malfunction of the ubiquitin proteasome system contributes to the pathogenesis of disease. The recent identification of four molecular chaperones, in addition to five previously identified chaperones, have provided mechanistic insight into how this cellular megastructure is assembled in the cell. These data, together with new insights into the structure and function of the proteasome, provide a much better understanding of this complex protease.

C Termini of Proteasomal ATPases Play Nonequivalent Roles in Cellular Assembly of Mammalian 26 S Proteasome

“…We utilized the epitope tag to monitor the steady-state incorporation of these proteins into 26 S proteasome and/or other pro- 2 The abbreviations used are: AMC, 7-amino-4-methylcoumarin; Suc, succinyl. tein complexes by glycerol density gradient centrifugation, as described above for endogenous proteins.…”

Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome

“…The lid partially surrounds the ATPase ring of the base, and two ubiquitin receptors, Rpn10 and Rpn13, are located on the periphery of the 19S RP [5][6][7][8] . Recent studies have suggested that the assembly of the proteasome proceeds via a highly ordered multistep mechanism [9][10][11][12] . All of the subcomplexes of the proteasome (CP, base, and lid) seem to assemble independently; the CP and base require multiple proteasome-dedicated chaperones for efficient and correct assembly.…”

The Levinthal paradox of the interactome

“…Successful self-assembly conditions had to be carefully worked out for the bacterial ribosome, 17,29 and corresponding conditions are unattainable for the eukaryotic ribosome, which requires as many as 200 accessory proteins in vivo, most of them essential. 30 Even lesscomplicated complexes, such as the nucleosome 31 or the proteasome, 32 require assisted assembly in the cell. Such examples illustrate a basic difference between the in vitro assembly of 20 isolated components, each introduced in a specific order under controlled conditions, and their in vivo assembly amidst a sea of competing components.…”