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Communication between ClpX and ClpP during substrate processing and degradation

Nature Structural & Molecular Biology volume 11, pages 404–411 (2004)Cite this article

Abstract

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.

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Figure 1: Symmetry mismatch between ClpX and ClpP.
Figure 2: Properties of ClpX loopless.
Figure 3: An assay for ClpX-ClpP interaction in solution.
Figure 4: ClpX-ClpP affinity changes in an ATPase-dependent manner during substrate denaturation and translocation.
Figure 5: Modification of the ClpP active sites strengthens ClpX binding.
Figure 6: ClpP rescues the unfolding defects of ClpX mutants.
Figure 7: The ATP state of ClpX is required for strong ClpP interactions.
Figure 8: Model for the interaction of ClpX and ClpP.

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Acknowledgements

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.

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  1. 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

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

    Tania A Baker

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Joshi, S., Hersch, G., Baker, T. et al. Communication between ClpX and ClpP during substrate processing and degradation. Nat Struct Mol Biol 11, 404–411 (2004). https://doi.org/10.1038/nsmb752

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