Proteasomes in the Archaea: From structure to function

Survival of cells is critically dependent on their ability to rapidly adapt to changes in the natural environment no matter how >extreme= the habitat. An interplay between protein folding and hydrolysis is emerging as a centr al mechanism for stress survival and proper cell function. In eucaryotic ce lls, most proteins destined for destruction are covalently modified by the ubiquitin-system and then degraded in an energy-dependent mechanism by the 26S proteasome, a multicatalytic protease. The 26S proteasome is composed o f a 20S proteolytic core and 19S cap (PA700) regulator which includes six A AA(+) ATPase subunits. Related AAA(+) proteins and 20S proteasomes are foun d in the archaea and Gram positive actinomycetes. In general, 20S proteasom es form a barrel-shaped nanocompartment with narrow openings which isolate rather non-specific proteolytic active-sites to the interior of the cylinde r and away from interaction with cytosolic proteins. The proteasome-associa ted AAA(+) proteins are predicted to form ring-like structures which unfold substrate proteins for entry into the central proteolytic 20S chamber resu lting in an energy-dependent and processive destruction of the protein. Det ailed biochemical and biophysical analysis as well as identification of pro teasomes in archaea with developed genetic tools are providing a foundation for understanding the biological role of the proteasome in these unusual o rganisms.