1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Molecular mechanism of thermosensory function of human heat shock transcription factor Hsf1

  1. Nikolai Hentze
  2. Laura Le Breton
  3. Jan Wiesner
  4. Georg Kempf
  5. Matthias P Mayer  Is a corresponding author
  1. AbbVie Deutschland GmbH &Co. KG, Germany
  2. Zentrum für Molekulare Biologie der Universität Heidelberg, Germany
  3. Universität Heidelberg, Germany
Research Article
  • Cited 40
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Cite this article as: eLife 2016;5:e11576 doi: 10.7554/eLife.11576

Abstract

The heat shock response is a universal homeostatic cell autonomous reaction of organisms to cope with adverse environmental conditions. In mammalian cells this response is mediated by the heat shock transcription factor Hsf1, which is monomeric in unstressed cells and upon activation trimerizes, and binds to promoters of heat shock genes. To understand the basic principle of Hsf1 activation we analyzed temperature-induced alterations in the conformational dynamics of Hsf1 by hydrogen exchange mass spectrometry. We found a temperature-dependent unfolding of Hsf1 in the regulatory region happening concomitant to tighter packing in the trimerization region. The transition to the active DNA binding-competent state occurred highly cooperative and was concentration dependent. Surprisingly, Hsp90, known to inhibit Hsf1 activation, lowered the midpoint temperature of trimerization and reduced cooperativity of the process thus widening the response window. Based on our data we propose a kinetic model of Hsf1 trimerization.

Article and author information

Author details

  1. Nikolai Hentze

    NBE Analytical R&D, AbbVie Deutschland GmbH &Co. KG, Ludwigshafen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Laura Le Breton

    Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Jan Wiesner

    Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Georg Kempf

    Biochemiezentrum, Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Matthias P Mayer

    Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    For correspondence
    M.Mayer@zmbh.uni-heidelberg.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. David Ron, University of Cambridge, United Kingdom

Publication history

  1. Received: September 13, 2015
  2. Accepted: January 18, 2016
  3. Accepted Manuscript published: January 19, 2016 (version 1)
  4. Version of Record published: February 22, 2016 (version 2)

Copyright

© 2016, Hentze et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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