Protease Complexes


Proteolysis is one of the most widespread mechanisms for biological regulation, providing control over such diverse phenomena as cell cycle progression, programmed cell death, blood clotting, complement activation, antigen presentation, inflammation, nutrient utilization, long‐term memory, cell migration and circadian rhythms.

Keywords: proteasome; ATP‐dependent; cell cycle; cell death; blood clotting; ubiquitin

Figure 1.

Proteasomes from eukaryotes and archea. Magenta, regulatory complex; blue, core complex; green, slice surface; red dots, active sites; cyan dots, N‐termini. In Panels 1c and 2f, cyan indicates the residues visualized that are closest to the N‐termini (Thr13 and Ser11, respectively). (a) Electron micrograph of proteasome holoenzyme from a representative eukaryote (Xenopus laevis); (b) medial cut‐away view of the T. acidophilum proteasome core. The lumen is divided into three chambers, and the central chamber contains the peptidase active sites (red); (c) ribbon diagram of two T. acidophilum α subunits, showing the structure of the pore; (d) Cut‐away view of the S. cerevisiae proteasome core; (e) ribbon diagram of two S. cerevisiae α subunits (left: Pre10/Prs1; right: Pre9/Y13). The N‐termini of these subunits are shown to occlude the channel. Adapted from Larsen and Finley . © 1997, with permission from Elsevier.

Figure 2.

The core particle gate. (a) Top view of the inactive proteasome core particle. The α subunit N‐termini seal the gate into the proteolytic chamber; (b) top view of activated proteasome core particle after binding of PA26. By docking of PA26 on to the apical surface of the proteasome core particle the α subunit N‐termini are restructured to open the gate. Reprinted from Forster and Hill (2003). © 2003, with permission from Elsevier.

Figure 3.

HslVU and ClpAP proteases. (a) Electron micrograph of HslVU. The identity of the uppermost, asymmetrically distributed mass is unknown. Blue, HslV core particle; magenta, HslU regulatory particle; (b) cut‐away view of the crystal structure of HslV. Adapted with permission from Larsen and Finley ; (c) ribbon diagram of two HslV subunits. The C‐terminus has been truncated to reduce the image size. Adapted with permission from Larsen and Finley ; (d) electron micrograph of ClpAP. Each cap particle has a distal and proximal ring of mass density. These may correspond to the two ATPase domains of ClpA. Blue, ClpP core particle; magenta, ClpA regulatory particle; (e) cut‐away view of ClpP; (f) ribbon diagram of two ClpP subunits.

Figure 4.

Crystal structure of the HslVU holocomplex. The C‐termini of HslU dock into surface clefts of the apical surface of HslV. Adapted from Groll et al. . Reproduced with permission from Wiley‐VCH.

Figure 5.

Cut‐away views of compartmentalized ATP‐independent proteases. (a) Crystal structure of the tricorn protease with one subunit superimposed. Adapted from Groll et al. . Reproduced with permission from Wiley‐VCH. Note that in Figure 3a and b the 2‐fold symmetry of the image results from the placement of the section plane, which is not a symmetry plane. The red dots indicate the active site positions; (b) S. cerevisiae Gal6; (c) Bovine leucine aminopeptidase.



Dougan DA, Weber‐Ban E and Bukau B (2003) Targeted delivery of an ssrA‐tagged substrate by the adaptor protein SspB to its cognate AAA+ protein ClpX. Molecular Cell 12: 373–380.

Elsasser S and Finley D (2005) Delivery of ubiquitinated substrates to protein‐unfolding machines . Nature Cell Biology 7: 742–749.

Förster A, Masters EI, Whitby FG, Robinson H and Hill CP (2005) The 1.9 A structure of a proteasome‐11S activator complex and implications for proteasome‐PAN/PA700 interactions. Molecular Cell 18: 589–599.

Groll M, Bochtler M, Brandstetter H, Clausen T and Huber R (2005) Molecular machines for protein degradation. Chembiochem 6: 222–256.

Groll M, Ditzel L, Loewe J et al. (1997) Structure of 20S proteasome from yeast at 2.4 A resolution. Nature 386: 463–471.

Hanna J, Hathaway NA, Tone Y et al. (2006) Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell 127: 99–111.

Larsen CN and Finley D (1997) Protein translocation channels in the proteasome and other proteases. Cell 91: 431–434.

Liu CW, Li X, Thompson D et al. (2006) ATP binding and ATP hydrolysis play distinct roles in the function of 26S proteasome. Molecular Cell 24: 39–50.

Martin A, Baker TA and Sauer RT (2005) Rebuilt AAA+motors reveal operating principles for ATP‐fuelled machines. Nature 437: 1115–1120.

Prakash S, Tian L, Ratliff KS, Lehotzky RE and Matouschek A (2004) An unstructured initiation site is required for efficient proteasome‐mediated degradation. Nature Structural Molecular Biology 11: 830–837.

Smith DM, Kafri G, Cheng Y et al. (2005) ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins. Molecular Cell 20: 687–698.

Sousa MC, Trame CB, Tsuruta H et al. (2000) Crystal and solution structures of an HslUV protease‐chaperone complex. Cell 103: 633–643.

Further Reading

Förster A and Hill CP (2003) Proteasome degradation: enter the substrate. Trends in Cell Biology 13: 550–553.

Ito K and Akiyama Y (2005) Cellular functions, mechanism of action, and regulation of FtsH protease. Annual Review of Microbiology 59: 211–231.

Pickart CM and Cohen RE (2004) Proteasomes and their kin: proteases in the machine age. Nature Reviews. Molecular Cell Biology 5: 177–187.

Prakash S and Matouschek A (2004) Protein unfolding in the cell. Trends in Biochemical Sciences 29: 593–600.

Rechsteiner M and Hill CP (2005) Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors. Trends in Cell Biology 15: 27–33.

Sauer RT, Bolon DN, Burton BM et al. (2004) Sculpting the proteome with AAA(+) proteases and disassembly machines. Cell 119: 9–18.

Tsilibaris V, Maenhaut‐Michel G and Van Melderen L (2006) Biological roles of the Lon ATP‐dependent protease. Research in Microbiology 157: 701–713.

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Schmidt, Marion, and Finley, Daniel(Jul 2007) Protease Complexes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000643.pub2]