Abstract 2152 Regulated protein degradation by bacterial nanomachines

Regulated protein degradation is essential for protein homeostasis and must be tightly controlled as the process is irreversible. In bacteria AAA+ proteolytic machines such as Lon and ClpXP, are responsible for the bulk of regulated protein degradation. Loss of these proteases result in protein homeostasis defects and physiological consequences such as reduced stress tolerance. Proper balanced activity of these proteases is therefore critical for maintaining cellular health. The Lon protease is especially subject to a variety of controlling factors, including adaptors, activators, inhibitors, and nucleotide levels. Newly characterized allosteric mechanisms, such as nucleic acid binding, novel regulators found through genome wide studies, and conserved mechanisms to couple ATP hydrolysis to protein degradation all result in robust on demand protein degradation to manage stress responses. Our recent efforts in understanding proteolytic machines will be described. Funding provided by NIGMS.