Structural Insights into Substrate Recognition and Processing by the 20S Proteasome

Four decades of proteasome research have yielded extensive information on ubiquitin-dependent proteolysis. The archetype proteasomes is a 20S barrel-shaped complex that does not rely ubiquitin as degradation signal but can degrade substrates with considerable unstructured stretch. Since roughly half all in most eukaryotic cells are free complexes, ubiquitin-independent protein may coexist by the highly regulated 26S proteasome. This article reviews recent advances our understanding biochemical and structural features underlie proteolytic mechanism proteasomes. two outer α-rings provide number potential docking sites for loosely folded polypeptides. binding substrate induce asymmetric conformational changes, trigger gate opening, initiate its own through protease-driven translocation mechanism. Consequently, translocates additional narrow apertures augmented β-catalytic active sites. overall pulling force annuli results protease-like unfolding subsequent proteolysis catalytic chamber. Although both contain identical sites, differential mechanisms yield distinct peptide products. Nonoverlapping repertoires product outcomes rationalize cohabitation complexes cells.