Proteasome & other proteases. 19-1. Proteasome - core complex and regulatory cap Other proteases - HslUV, ClpAP, ClpXP, Lon, FtsH. The proteasome. eukaryotic proteasome seven types of alpha subunits seven types of beta subunits regulatory cap (at least 17 subunits).
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- core complex and regulatory cap
- HslUV, ClpAP, ClpXP, Lon, FtsH
core particle (20S)
regulatory particle (19S)
core particle (20S)
Proteasomes from eukaryotes and archaea, showing the cap complex (magenta), core complex (blue, where alpha and beta subunits are shown), slice surface (green), active sites (white circles) and N-termini (circled ‘N’s). In (c) and (f), cyan indicates the residues visualized that are closest to the N-termini (threonine 13 and serine 11 respectively). (a) Electron micrograph of proteasome holoenzyme from a representative eukaryote (Xenopus laevis). (b) Medial cut-away view of the Thermoplasma 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 Thermoplasma acidophiluma subunits, showing the structure of the pore. (d) Cut-away view of the Saccharomyces cerevisiae proteasome core. (e) Ribbon diagram of two S. cerevisiaea subunits (left: Pre9/Y13; right: Pre10/Prs1). The N-termini of these subunits are shown to occlude the channel. Adapted from Dan Finley, Encylopedia of Life Sciences.
with 11S regulator particle
its repertoire of substrates likely includes other cellular proteins
structures of 2 subunits;
superimposable to the beta
subunits of the archaeal
inside view of
Figure 1 Comparison of different classes of ATP-dependent pro- teases, shown as a side-on cross-section. (A) The eukaryotic 26S proteasome, composed of a 20S core particle (blue a and b subunits) flanked by 19S regulatory subunits (magenta and orange). The 19S subunits bind to the substrate through the covalent ubiquitin modification (yellow) and unfold it by pulling on the unstructured initiation site (bright green). Ubiquitin is removed to be recycled during the degradation process. (B) The bacterial protease ClpXP, composed of rings of the protease ClpP (dark green) and the ATPase motor ClpX (red). ClpX binds to the degradation signal, in this case the ssrA peptide sequence (green), which also serves as the site for the initiation of degradation. (C) The actinobacterial proteasome, consisting of a 20S core particle similar to that of the 26S proteasome, and a single ring of the ATPase Mpa (purple). Mpa binds to the substrate through the covalent Pup modification (light green). Pup has an N-terminal unstructured region, which serves as the site for the initiation of degradation, leading to complete degradation of Pup. (D) Archaeal proteasome is most closely related to the eukaryotic proteasome, with core alpha and beta subunits and Rpt-like AAA ATPase subunits (termed PAN for Proteasome Activating Nucleotidase) involved in protein unfolding.
Kraut and Matouschek EMBO J. 2009
(similar to how Hsp104 from yeast can disentangle protein aggregates)
ClpAP, ClpXP are ‘active’ proteases
ClpP by itself not active as protease
- ClpP (2 rings) has
- ClpA, ClpX attach
As single rings on
Opposite sides of ClpP
next lecture: evidence for ClpA unfolding
- e.g., proteasome, HslUV, ClpAP/XP, Tricorn protease, etc.