Figure 5

Proteasome evolution showing step-wise increase in complexity, first to the HslV ring protease, then to the 20S proteasome, and lastly to the 26S proteasome; the two major transitions in proteasome structure important for polarizing the tree are marked by grey bars. Blue bars mark four other important evolutionary transitions that also congruently polarize the tree. HslV has 6-fold symmetry (a 2-tiered ring of 12 identical subunits) and arose from a monomeric NTN hydrolase, probably just before Hadobacteria diverged. HslV rings interact with an unrelated chaperone ATPase, HslU, also having 6-fold ring symmetry, like ClpX chaperone from which it arguably evolved and virtually all AAA+ ATPase proteins, which originated in a burst of gene duplications prior to the last common ancestor of all life [19]. The 4-tier proteolytic core of the 6-tiered 20S proteasome evolved in a common ancestor of neomura and Actinomycetales (jointly proteates) of the subphylum Actinobacteria by another gene duplication that generated its catalytic β- and non-catalytic α-subunits from HslV, with an associated symmetry change to 7-fold: all four rings forming the core of the proteasomal cylinder have 7 subunits, but the 6-fold-symmetric HslU was replaced by another hexameric ATPase ring from a different AAA+ family to make the proteasome 'base' (red in the two-colour sketch of the archaebacterial proteasome at the top left). Glycobacteria [1] comprise all the typical negibacteria with OM lipopolysaccharide, i.e. all negibacterial phyla listed in Table 2 except Hadobacteria and Chlorobacteria).