Eukaryotic cells contains thousands of different proteins, many of which are required for only brief periods during the cellular cycle. These short-lived proteins, along with any misfolded or damaged intracellular proteins, are destroyed by a large proteolytic complex named the 26S proteasome. This complex consists of about 32 different subunits, which form a barrel-shaped 20S peptidase that is capped at one or both ends by a 19S regulatory particle. Unwanted cellular proteins are marked for degradation by covalent attachment of a polyubiquitin chain, which is recognized by the 19S regulatory particle. The 19S particle is also responsible for subsequent deubiquitination and unfolding of the targeted substrate, and contains a AAA+ ATPase that translocates the unfolded substrate into the 20S proteolytic chamber. In collaboration with the Andreas Martin, whose lab has developed a novel expression system for reconstituting the 19S regulatory particle, we solved the structure of the yeast 26S proteasome to subnanometer resolution, localizing all the constitutive components. This understanding of the structural organization of the 19S regulatory particle relative to 20S offers insight into the manner in which the 19S performs and coordinates its many functions. Combining these new structural findings with the biochemical expertise of the Martin lab, we plan on furthering our mechanistic understanding of this molecular machine's regulatory role in cellular homeostasis.