Studies on the eukaryotic proteasome have revealed that several chaperones are required for it successful assembly. Proteasome assembly chaperones (PACs) work in a sequence, with PAC1-PAC2 dimer and the PAC3-PAC4 dimer acting on a subunits to form the heptameric a-rings. Then the 6 ß subunits come in to form a half proteosome complex with the a-rings, releasing the Pac3-Pac4 chaperones; the place of the 7th subunit is occupied by the Ump1 chaperone. Finally the 7th subunit is added which dimerizes the two half proteasomes to complete the structure. At this point the proteasome is activated by autocatalytic maturation of the ß subunits. It then degrades Pac1-Pac2 and Ump1. While the origin of the proteasome itself is traced back to the simple proteasomal precursor found in the archaea, the origin of the chaperone system remained mysterious. Thus far none of the chaperones have been found in archaea or the bacterial proteasomal systems acquired from the archaea.
We discovered that an ortholog of the eukaryotic PAC2 (e.g. Corynebacterium cg2106, PBD: 2p90) is often present in the vicinity of the actinobacterial Pup-proteasome gene-neighborhoods and some archaeal proteasomal ATPase gene-neighborhoods. Most bacteria and archaea encode two Pac2 paralogs. The structure of Cg2106 suggests that PAC2 forms a trimeric torroid. Hence it might provide a scaffold for assembly of proteasomal peptidase subunits. As none of the other eukaryotic proteasomal chaperones have orthologs in archaea or bacteria, this protein is likely to represent the ancestral chaperone of the proteasome. Thus, for the first time we find evidence for a eukaryote-type proteasomal assembly process in the prokaryotes, which possibly operated on the a subunits even there.
For more details, you can read the open access version of the paper. Click here to access it. You can also access the Pac2 alignment and operons in our supplementary material to the above paper. Please click here to access it.