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Review
. 2014 Jan;1843(1):2-12.
doi: 10.1016/j.bbamcr.2013.03.008. Epub 2013 Mar 16.

Assembly of the 20S proteasome

Mary J Kunjappu  1 , Mark Hochstrasser
Affiliations
Review

Assembly of the 20S proteasome

Mary J Kunjappu et al. Biochim Biophys Acta. 2014 Jan.

Abstract

The proteasome is a cellular protease responsible for the selective degradation of the majority of the intracellular proteome. It recognizes, unfolds, and cleaves proteins that are destined for removal, usually by prior attachment to polymers of ubiquitin. This macromolecular machine is composed of two subcomplexes, the 19S regulatory particle (RP) and the 20S core particle (CP), which together contain at least 33 different and precisely positioned subunits. How these subunits assemble into functional complexes is an area of active exploration. Here we describe the current status of studies on the assembly of the 20S proteasome (CP). The 28-subunit CP is found in all three domains of life and its cylindrical stack of four heptameric rings is well conserved. Though several CP subunits possess self-assembly properties, a consistent theme in recent years has been the need for dedicated assembly chaperones that promote on-pathway assembly. To date, a minimum of three accessory factors have been implicated in aiding the construction of the 20S proteasome. These chaperones interact with different assembling proteasomal precursors and usher subunits into specific slots in the growing structure. This review will focus largely on chaperone-dependent CP assembly and its regulation. This article is part of a Special Issue entitled: Ubiquitin-Proteasome System. Guest Editors: Thomas Sommer and Dieter H. Wolf.

Keywords: Assembly factors; Macromolecular complex assembly; Proteasome; Proteolysis; Ubiquitin-proteasome system.

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Figures

Figure 1
Figure 1. Structural features of the Eukaryotic 20S Proteasome
A. An electron micrograph structure of the 26S proteasome (grey) from yeast with the 20S (CP) and 19S (RP) labeled. The yeast CP crystal structure is shown with each subunit colored. B. In the top panel, a clipped structure of the CP on its side illustrates three of the six catalytically active sites shown as red spheres. The bottom panel highlights the three linked chambers within the proteasome. C. The occluded pore of the CP (grey with individual subunits colored) from wild type cells is juxtaposed with the open pore from the α3ΔN strain indicated by an arrow. All images were made using PyMol or Chimera using structures elucidated in Refs [15, 29].
Figure 2
Figure 2. Model for the assembly of the Eukaryotic CP
This cartoon depicts assembly precursors that were isolated, or shown to form, in yeast. I. α (blue) and β subunits with propeptides (red) are synthesized as free polypeptides. An α ring is formed initially with the aid of the Pba3/4 (red and orange) chaperone that interacts specifically with the α5 subunit. II. The isolated 15S intermediate contains a full α ring, the β2, β3 and β4 subunits and two assembly chaperones: Pba1/2 (blue and green) and Ump1 (yellow). III. The –β7 intermediate is composed of a full complement of subunits except the β7 subunit and Pba1/2 and Ump1. IV. The half-proteasome has a full α ring and full β ring, but is still associated with the assembly chaperones Pba1/2 and Ump1. V. The dimerization of the half-proteasomes forms the preholoproteasome that is still immature. VI. CP maturation is achieved by the autocatalytic processing of the β subunit propeptides and the degradation of the Ump1 chaperone. The Pba1/2 chaperone is also released upon maturation. This process yields a functional CP competent for protein degradation.
Figure 3
Figure 3. C-terminal extensions of the β2 and β7 subunits serve to stabilize the assembling CP
The β2 subunit (green) forms extensive contacts with the β3 subunit through its C-terminal extension. The C-terminal 30 amino acid residues are shown here in magenta. The β7 subunit (dark yellow) inserts its C-terminal extension between the β2 and β1 subunit of the opposing β ring. The final 15 amino acids residues of β7 are shown in red. The image was made using PyMol using the structure elucidated in Refs [15].
Figure 4
Figure 4. Assembly chaperones Pba1 and Pba2 associate with the CP α ring
Pba1 (purple) and Pba2 (orange) interact with intra-α subunit pockets of the 20S (grey) through their C-terminal HbYX motifs. The image was made using PyMol using the structure elucidated in Refs [67].
Figure 5
Figure 5. Proteasome biogenesis associated (Pba) factors 3 and 4
A. The structure of the Pba3/4 dimer is similar to the structure of proteasome subunits. A representative α subunit is shown for comparison. Helices are indicated in red, β strands in yellow and loops in green. B. The Pba3 (blue) and Pba4 (green) chaperone associates with the α5 subunit (purple) in such a manner that there is a steric clash with the β4 subunit (yellow) unless Pba3/4 disassociates before this subunit is incorporated into the CP. These images were made using PyMol using structures elucidated in Refs [15, 69].
Figure 6
Figure 6. The HEAT repeat protein, Blm10, caps the CP
A. Blm10 (orange) occupies surfaces that are usually bound by regulators of the CP (grey). A top-down view of the Blm10 (orange) capped CP (grey) reveals a narrow opening through the proteasome, indicated here by an arrow. These images were made using PyMol using the structure elucidated in Refs [78].
See this image and copyright information in PMC

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