Proteasome Activation

The proteasome is a protease that performs most of the proteolysis that occurs in the eukaryotic cytosol and nucleus, and is required for many (perhaps most) facets of cellular function. It's impressive barrel-shaped architecture of 28 subunits and ~700 kDa houses proteolytic sites in the hollow interior. Substrates access the proteolytic sites through channels in the center of the alpha rings that are closed in the absence of an activator. We are characterizing proteasome activators by a combination of x-ray crystal structure determination, protein biochemistry, and yeast genetics (collaboration with Tim Formosa). We are also identifying new binding partners that utilize the same binding mode as established activators and may perform a range of biological functions.