Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Chaperones

Speedy motion for function

Nature Chemical Biology volume 12, pages 576–577 (2016)Cite this article

Subjects

Hsp90 is an energy-consuming molecular chaperone that activates oncogenic proteins in a complicated multi-step reaction. Photoinduced electron transfer (PET) quenching experiments with a fluorescent reporter have now identified molecular transitions at multiple timescales in the chaperone cycle of Hsp90.

Molecular chaperones are crucial guardians of protein homeostasis within cells. By binding to their client proteins, they typically prevent aggregation and/or facilitate folding. Hsp90 is a unique member of this diverse class of proteins because it stabilizes many key cellular regulators and signal transducers. As a downside, however, Hsp90 may rescue destabilizing mutations in its client proteins that otherwise would be lethal, thus facilitating tumorigenesis1. A large body of biochemical, structural, and biophysical work has therefore been dedicated to unravel the mechanism by which Hsp90 works. In their recent study, Schulze et al. now add a new dimension to this mechanism by detecting internal motions during the reaction cycle of this machine at timescales from microseconds to minutes2.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Cycling between open and closed states.

Accession codes

Accessions

Protein Data Bank

References

  1. Whitesell, L. & Lindquist, S.L. Nat. Rev. Cancer 5, 761–772 (2005).

    Article  CAS  Google Scholar 

  2. Schulze, A. et al. Nat. Chem. Biol. 12, 628–635 (2016).

    Article  CAS  Google Scholar 

  3. Hessling, M., Richter, K. & Buchner, J. Nat. Struct. Mol. Biol. 16, 287–293 (2009).

    Article  CAS  Google Scholar 

  4. Mickler, M., Hessling, M., Ratzke, C., Buchner, J. & Hugel, T. Nat. Struct. Mol. Biol. 16, 281–286 (2009).

    Article  CAS  Google Scholar 

  5. Ratzke, C., Mickler, M., Hellenkamp, B., Buchner, J. & Hugel, T. Proc. Natl. Acad. Sci. USA 107, 16101–16106 (2010).

    Article  CAS  Google Scholar 

  6. Sauer, M. & Neuweiler, H. in Fluorescence Spectroscopy and Microscopy: Methods and Protocols 597–615 (Humana Press, Clifton, NJ, USA, 2014).

    Book  Google Scholar 

  7. Onsager, L. Phys. Rev. 37, 405–426 (1931).

    Article  CAS  Google Scholar 

  8. Taipale, M., Jarosz, D.F. & Lindquist, S. Nat. Rev. Mol. Cell Biol. 11, 515–528 (2010).

    Article  CAS  Google Scholar 

  9. Neckers, L. & Workman, P. Clin. Cancer Res. 18, 64–76 (2012).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hagen Hofmann is in the Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.,

    Hagen Hofmann

Authors
  1. Hagen Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hagen Hofmann.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hofmann, H. Speedy motion for function. Nat Chem Biol 12, 576–577 (2016). https://doi.org/10.1038/nchembio.2130

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.2130

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing