Wiggle and Shake: Managing and Exploiting Conformational Dynamics during Proteasome Biogenesis

The 26S proteasome is the largest and most complicated protease known, changes to assembly or function contribute numerous human diseases. Assembly of from its ~66 individual polypeptide subunits a highly orchestrated process requiring concerted actions both intrinsic elements subunits, as well assistance by extrinsic, dedicated chaperones. With advent near-atomic resolution cryo-electron microscopy, it has become evident that dynamic machine, undergoing conformational in response ligand binding during proteolytic cycle. In contrast, an appreciation role dynamics biogenesis only recently begun emerge. Herein, we review our current knowledge assembly, with particular focus on how guide events. Furthermore, highlight key emerging questions this rapidly expanding area.