Melissa Gräwert

So far my major research interests have been the interactions between biological macromolecules that I have analyzed structurally and biophysically. Protein interactions are the fundamental driving force of almost every cellular process. Protein-Protein Interactions (PPIs) play an important role in cell cycle control, signal transduction and intermediary metabolism just to name a few. Thus, it is important to look beyond the function of every single gene product and to additionally understand how the ensemble of these gene products, subassemblies, and regulatory networks act together in highly evolved organisms. Macromolecular X-ray crystallography (MX) is a very important tool for these studies. This high resolution technique allows the visualization of interactions at an atomic level. From this, conclusions on binding affinities, forces and specificity can be derived. During my postdoctoral fellowship in Michael Groll’s lab, I was deeply involved in setting up and running our state-of-the-art X-ray core facility comprising an in-house X-ray generator and robotics for setting up crystallization trials. This infrastructure allowed us to grow many crystals and more importantly obtain high resolution structures that tell us fascinating stories. For example, co-crystallization of the 700 kDa proteasome from baker’s yeast with ligands resulted in important new structures with potential application as anti-cancer drugs. One of these gave insights into a new mode of proteasome inhibition by α-keto-aldehydes explaining their low levels of cross reactions and thus, reduced toxicity.