Cottrell College Science Awards - 2015
Do Proteasomal Motor Proteins Have Separable Functions? The Effect of Aromatic Paddle Mutations on Proteasomal Processivity
Each of the billions of cells in our bodies requires many different forms of protein to do its work. Each cell has to make flawless versions of these proteins, and, when the proteins have fulfilled their duties or become diseased and no longer function properly, the cell must recycle them.
Breaking down proteins is as essential to a cell’s health as its ability to make them. Proteasomes are the cell's protein recyclers.
Daniel A. Kraut, assistant professor of chemistry at Villanova University, has received a Cottrell College Science Award from Research Corporation for Science Advancement to further our understanding on how this biological machine, the proteasome, functions to unfold and degrade proteins. It is hoped his work will also shed additional light on the mechanism by which some proteins escape complete degradation and are instead released as partially degraded fragments.
Kraut and his students will study proteasomes from yeast cells, which, like human cells, are classified as eukaryotic – a term indicating they have a nucleus and other organelles enclosed within a membrane. Kraut has developed an assay – a test procedure – that allows him to judge how fast the proteasome unfolds and degrades proteins versus how fast proteins irreversibly fall away from this process.
Specifically, they will investigate the individual roles and coordination of the six distinct subunits of the proteasome’s “ATPase motor.” ATP is the molecule that fuels the various functions of the cell; an “ATPase” is enzyme that catalyzes the formation of ATP. Kraut theorizes that ATPases likely play specialized roles in the movement and function of the eukaryotic proteasome. He believes they provide the molecular “muscle” allowing the proteasome to steady and then pull apart its target proteins.
If successful, Kraut’s work could have important implications for understanding the cell’s life cycle, apoptosis (cell death), and perhaps even a major contributing factor for many diseases, including cancer and neurodegenerative diseases.