Prokaryotic proteasomes: nanocompartments of degradation

Abstract

Proteasomes are self-compartmentalized energy-dependent proteolytic machines found in Archaea, Actinobacteria species of bacteria and eukaryotes. Proteasomes consist of two separate protein complexes, the core particle that hydrolyzes peptide bonds and an AAA+ ATPase domain responsible for the binding, unfolding and translocation of protein substrates into the core particle for degradation. Similarly to eukaryotes, proteasomes play a central role in protein degradation and can be essential in Archaea. Core particles associate with and utilize a variety of ATPase complexes to carry out protein degradation in Archaea. In actinobacterial species, such as Mycobacterium tuberculosis, proteasome-mediated degradation is associated with pathogenesis and does not appear to be essential. Interestingly, both actinobacterial species and Archaea use small proteins to covalently modify proteins, prokaryotic ubiquitin-like proteins (Pup) in Actinobacteria and ubiquitin-like small archaeal modifier proteins (SAMP) in Archaea. These modifications may play a role in proteasome targeting similar to the ubiquitin-proteasome system in eukaryotes.

Fig. 1

20S core particle: three views and dimensions. a 20S core particle from T. acidophilium (PDB 1PMA) consisting of a stack of heptameric rings of α- and β-type subunits arranged as α₇β₇β₇α₇. b Cross-sectional view of T. acidophilium 20S core particle displaying antechambers and degradation chambers within the structure. c Axial view of 20S core particle in ‘closed’ conformation with an obstructed axial channel leading into the antechamber (PDB 3C92).

Fig. 2

Regulatory ATPases. Hexameric ATPase complexes activate protease activity of 20S proteasomes through interaction with the outer α-rings of the proteasome and the HbYX C-terminal motif on the ATPase. Variation in the N-domains between the different ATPases may influence substrate binding of those complexes.

Fig. 3

Pupylation and sampylation pathways. a Pupylation pathway in M. tuberculosis for the deamidation, ligation and depupylation of proteasome substrates for degradation. b Sampylation pathway for the adenylation (activation), ligation to substrates and desampylation for possible degradation by proteasomes.