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Molecular determinants of complex formation between Clp/Hsp100 ATPases and the ClpP peptidase

Nature Structural Biology volume 8, pages 230–233 (2001)Cite this article

Abstract

The Clp/Hsp100 ATPases are hexameric protein machines that catalyze the unfolding, disassembly and disaggregation of specific protein substrates in bacteria, plants and animals. Many family members also interact with peptidases to form ATP-dependent proteases. In Escherichia coli, for instance, the ClpXP protease is assembled from the ClpX ATPase and the ClpP peptidase. Here, we have used multiple sequence alignments to identify a tripeptide 'IGF' in E. coli ClpX that is essential for ClpP recognition. Mutations in this IGF sequence, which appears to be part of a surface loop, disrupt ClpXP complex formation and prevent protease function but have no effect on other ClpX activities. Homologous tripeptides are found only in a subset of Clp/Hsp100 ATPases and are a good predictor of family members that have a ClpP partner. Mapping of the IGF loop onto a homolog of known structure suggests a model for ClpX–ClpP docking.

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Figure 1: Position of the proposed ClpP interaction loop in the ClpX and ClpA subfamilies.
Figure 2: ClpX mutants are active chaperones but defective in proteolysis.
Figure 3: ClpXI268E and ClpXF270W are defective in ClpP interaction.
Figure 4: Model for the location of the ClpP interaction loop based on the HslU structure.

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Acknowledgements

We thank E. Beade for preparation of Fig. 4b, L. Roldan for assistance with figures, and N. Murray for advice on the restriction alleviation assay. This work was supported by an NIH grant and the Howard Hughes Medical Institute.

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  1. Yong-In Kim and Igor Levchenko: These authors contributed equally to this work.

Authors and Affiliations

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

    Yong-In Kim, Igor Levchenko, Karolina Fraczkowska, Rachel V. Woodruff, Robert T. Sauer & Tania A. Baker

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

    Yong-In Kim, Igor Levchenko & Tania A. Baker

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Correspondence to Tania A. Baker.

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Kim, YI., Levchenko, I., Fraczkowska, K. et al. Molecular determinants of complex formation between Clp/Hsp100 ATPases and the ClpP peptidase. Nat Struct Mol Biol 8, 230–233 (2001). https://doi.org/10.1038/84967

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