Title: "Proteome-wide investigation of conformational energy landscapes of proteins by proteolysis"
Speaker: Chiwook Park, Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University
Place: Mechanical Engineering (ME) 161; Tuesday, 4:30pm


Native states of proteins are dynamic, populating more than just the unique native conformation. The population of each conformation and the rates of dynamic interconversion between them define a protein's conformational energy landscape. Information on this conformational energy landscape has been shown to be quite useful in studying protein?ligand interactions as well as in understanding protein folding and dynamics. Proteolytic susceptibility is one feature determined by this conformational energy landscape; unless the native conformation has an unstructured region, proteases cannot effectively digest a protein under native conditions. To analyze the conformational energy landscapes of proteins in a high-throughput fashion, proteolysis was employed as a conformational probe. First, by studying proteolysis kinetics of RNase H in the native state, we demonstrated that proteolysis can probe high-energy states of this protein. Proteolysis of this protein was found to occur through local fluctuation in the native conformation without experiencing global unfolding. Next, to show that proteolysis can be used to study the energetics of proteins on a proteomic scale, we challenged the E. coli proteome with extensive proteolysis and identified a handful of survivors which have optimized energy landscapes for this unusual resistance to proteolysis. These studies show that proteolysis is a versatile structural probe for proteome-wide investigation of conformational energy landscapes of proteins.

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