Speaker
Description
Molecular motors transduce chemical energy –usually from ATP hydrolysis– into directed motion and mechanical work, which is used to perform key functions in almost every cellular process. Molecular motors are particularly important in the maintenance of cellular proteostasis, i.e. the equilibrium between protein synthesis and degradation. ATP-dependent proteases of the AAA+ family, such as ClpXP from Escherichia coli and the eukaryotic 26S proteasome, play a central role in protein degradation. Given its extensive biochemical and structural characterization, ClpXP is a paradigm for the study of the operating principles of eukaryotic and prokaryotic protease machines of the AAA+ family. However, the molecular mechanism by which ClpXP couples the energy from ATP hydrolysis into mechanical work is still poorly understood. Here we used biochemical and single-molecule assays with optical tweezers to directly probe the operation of ClpXP as it unfolds and translocates its protein substrate. We observe that ClpXP operates with constant “rpm” but uses different “gears”, and provide insights about how evolution has tuned the structure and sequence of this motor to maximize its power production and mechanical efficiency.
