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Allostery in the Hsp70 Chaperone Proteins

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Molecular Chaperones

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 328))

Abstract

Heat shock 70-kDa (Hsp70) chaperones are essential to in vivo protein folding, protein transport, and protein re-folding. They carry out these activities using repeated cycles of binding and release of client proteins. This process is under allosteric control of nucleotide binding and hydrolysis. X-ray crystallography, NMR spectroscopy, and other biophysical techniques have contributed much to the understanding of the allosteric mechanism linking these activities and the effect of co-chaperones on this mechanism. In this chapter these findings are critically reviewed. Studies on the allosteric mechanisms of Hsp70 have gained enhanced urgency, as recent studies have implicated this chaperone as a potential drug target in diseases such as Alzheimer’s and cancer. Recent approaches to combat these diseases through interference with the Hsp70 allosteric mechanism are discussed.

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Acknowledgements

Support from NIH grants GM63027-S02 (ERPZ, AA), NS059690 (AR, ERPZ and JEG) is gratefully acknowledged. An anonymous reviewer is gratefully acknowledged for suggesting many improvements to the manuscript.

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Authors and Affiliations

  1. Department of Biological Chemistry, The University of Michigan, Ann Arbor, MI, 48109, USA

    Erik R. P. Zuiderweg, Eric B. Bertelsen, Jason E. Gestwicki & Atta Ahmad

  2. Program in Biophysics, The University of Michigan, Ann Arbor, MI, 48109, USA

    Aikaterini Rousaki

  3. Institute of Organic Chemistry and Chemical Biology, Goethe University, Max-von-Laue-Str. 7, 60438, Frankfurt, DE

    Aikaterini Rousaki

  4. Zentrum für Molekulare Biologie der Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany

    Matthias P. Mayer

  5. Lifesciences Institute, The University of Michigan, Ann Arbor, MI, 48109, USA

    Jason E. Gestwicki & Atta Ahmad

  6. Department of Pathology, The University of Michigan, Ann Arbor, MI, 48109, USA

    Jason E. Gestwicki

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  1. Erik R. P. Zuiderweg
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Correspondence to Erik R. P. Zuiderweg .

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    Sophie Jackson

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Zuiderweg, E.R.P., Bertelsen, E.B., Rousaki, A., Mayer, M.P., Gestwicki, J.E., Ahmad, A. (2012). Allostery in the Hsp70 Chaperone Proteins. In: Jackson, S. (eds) Molecular Chaperones. Topics in Current Chemistry, vol 328. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_323

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