细胞期刊(Cell)2013-10-28 11:40 PM

The ClpXP Protease Unfolds Substrates Using a Constant Rate of Pulling but Different Gears

Highlights
- At least two ClpX subunits must bind and hydrolyze ATP for substrate translocation
- Coordinated firing of two, three, or four subunits drives rapid translocation “bursts”
- The time between translocation bursts is independent of the ATP occupancy of ClpX
- Translocation occurs upon the phosphate release step of the ATPase cycle
Summary
ATP-dependent proteases are vital to maintain cellular protein homeostasis. Here, we study the mechanisms of force generation and intersubunit coordination in the ClpXP protease from E. coli to understand how these machines couple ATP hydrolysis to mechanical protein unfolding. Single-molecule analyses reveal that phosphate release is the force-generating step in the ATP-hydrolysis cycle and that ClpXP translocates substrate polypeptides in bursts resulting from highly coordinated conformational changes in two to four ATPase subunits. ClpXP must use its maximum successive firing capacity of four subunits to unfold stable substrates like GFP. The average dwell duration between individual bursts of translocation is constant, regardless of the number of translocating subunits, implying that ClpXP operates with constant “rpm” but uses different “gears.”

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细胞期刊(Cell)

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