Communication between ClpX and ClpP during substrate processing and degradation

In the ClpXP compartmental protease, ring hexamers of the AAA+ ClpX ATPase bind, denature and then translocate protein substrates into the degradation chamber of the double-ring ClpP14

peptidase. A key question is the extent to which functional communication between ClpX and ClpP occurs and is regulated during substrate processing. Here, we show that ClpX-ClpP affinity

varies with the protein-processing task of ClpX and with the catalytic engagement of the active sites of ClpP. Functional communication between symmetry-mismatched ClpXP rings depends on the

ATPase activity of ClpX and seems to be transmitted through structural changes in its IGF loops, which contact ClpP. A conserved arginine in the sensor II helix of ClpX links the nucleotide

state of ClpX to the binding of ClpP and protein substrates. A simple model explains the observed relationships between ATP binding, ATP hydrolysis and functional interactions between ClpX,

protein substrates and ClpP.

We thank S. Boyd, R. Burton, E. Courtenay, C. Farrell, J. Flynn, R. Grant, J. Kenniston, I. Levchenko, S. Siddiqui and D. Wah for discussion and materials, R. Horvitz and J. King for use of

equipment and D. Kim and K. Kim (Sungkyunkwan University School of Medicine, Korea) for the ClpX hexamer coordinates. This work was supported by grants from the US National Institutes of

Health and the Howard Hughes Medical Institute (HHMI). T. Baker is an employee of HHMI.

Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

Shilpa A Joshi, Greg L Hersch, Tania A Baker & Robert T Sauer

Howard Hughes Medical Institute, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

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