Evolution of the ubiquitin-like modifications and proteasomal degradation systems in the archaea

The modification of protein substrates by ubiquitin regulates a diverse range of critical biological functions including targeting of substrates to the proteasome for degradation. Ubiquitin-like modifications have also been described in the archaeal domain of life. It has subsequently been hypothesized that ubiquitin-like proteasomal degradation might also operate in these microbes, since all archaeal species utilize homologues of the eukaryotic proteasome. Structural and biochemical analyses of a ubiquitin-like modification pathway in the archaeon Sulfolobus acidocaldarius will be presented to demonstrate that modified substrates are recognized and processed by the archaeal proteasome, by virtue of a direct interaction with the modifier. Furthermore, although it has been established that ubiquitin-like modifiers evolved from prokaryotic sulphur transfer proteins it is less clear how complex eukaryotic ubiquitylation system arose and diversified from these prokaryotic antecedents. The discovery of ubiquitin, E1-like, E2-like and small-RING finger (srfp) protein components in the Aigarchaeota and the Asgard archaea superphyla has provided a substantive step toward addressing this evolutionary question. A biochemical reconstitution of these proteins from the archaeon Candidatus ‘Caldiarchaeum subterraneum’ will also be presented revealing that these components operate together as a bona fide ubiquitin modification system, mediating a sequential ubiquitylation cascade reminiscent of the eukaryotic process.