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Tuning of chaperone activity of Hsp70 proteins by modulation of nucleotide exchange

Nature Structural Biology volume 8, pages 427432 (2001) | Download Citation

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Abstract

The Hsp70 chaperone activity in protein folding is regulated by ATP-controlled cycles of substrate binding and release. Nucleotide exchange plays a key role in these cycles by triggering substrate release. Structural searches of Hsp70 homologs revealed three structural elements within the ATPase domain: two salt bridges and an exposed loop. Mutational analysis showed that these elements control the dissociation of nucleotides, the interaction with exchange factors and chaperone activity. Sequence variations in the three elements classify the Hsp70 family members into three subfamilies, DnaK proteins, HscA proteins and Hsc70 proteins. These subfamilies show strong differences in nucleotide dissociation and interaction with the exchange factors GrpE and Bag-1.

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Acknowledgements

We thank J. Höhfeld and R. Morimoto for plasmids expressing Bag-1M and Hsc70; A. Valencia and A. Buchberger for design and cloning of dnaK-K55A; T. Hesterkamp, A. Hoelz and T. Laufen for helpful discussions. This work was supported by grants of the DFG to J.R., and the DFG (Graduiertenkolleg Biochemie der Enzyme; Leibniz program) and the Fonds der Chemischen Industrie to B.B.

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Affiliations

  1. Institut für Biochemie und Molekularbiologie, Albert-Ludwigs-Universität Freiburg, Hermann-Herder-Str. 7, D-79104 Freiburg, Germany.

    • Dirk Brehmer
    • , Stefan Rüdiger
    • , Claudia S. Gässler
    • , Matthias P. Mayer
    •  & Bernd Bukau
  2. Cambridge Centre for Protein Engineering, MRC Centre, Hills Road, Cambridge CB2 2QH, UK.

    • Stefan Rüdiger
  3. The Scripps Research Institute, Department of Molecular Biology, MB-19, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

    • Dagmar Klostermeier
  4. Max-Planck-Institut für molekulare Physiologie, Abteilung physikalische Biochemie, Otto-Hahn-Str. 11, D-44227 Dortmund, Germany.

    • Dagmar Klostermeier
    • , Lars Packschies
    •  & Jochen Reinstein

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Correspondence to Bernd Bukau.

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DOI

https://doi.org/10.1038/87588

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