Head-to-tail interactions of the coiled-coil domains regulate ClpB cooperation with Hsp70 in protein disaggregation

  1. Marta Carroni
  2. Eva Kummer
  3. Yuki Oguchi
  4. Petra Wendler
  5. Daniel K Clare
  6. Irmgard Sinning
  7. Jürgen Kopp
  8. Axel Mogk
  9. Bernd Bukau
  10. Helen Saibil  Is a corresponding author
  1. Birkbeck College, University of London, United Kingdom
  2. Zentrum für Molekulare Biologie der Universität Heidelberg, Germany
  3. Ludwig-Maximilians-University Munich, Germany
  4. Biochemie-Zentrum der Universität Heidelberg (BZH), Germany

Abstract

The hexameric AAA+ chaperone ClpB reactivates aggregated proteins in cooperation with the Hsp70 system. Essential for disaggregation, the ClpB middle domain (MD) is a coiled-coil propeller that binds Hsp70. Although the ClpB subunit structure is known, positioning of the MD in the hexamer and its mechanism of action are unclear. We obtained electron microscopy (EM) structures of the BAP variant of ClpB that binds the protease ClpP, clearly revealing MD density on the surface of the ClpB ring. Mutant analysis and asymmetric reconstructions show that MDs adopt diverse positions in a single ClpB hexamer. Adjacent, horizontally oriented MDs form head-to-tail contacts and repress ClpB activity by preventing Hsp70 interaction. Tilting of the MD breaks this contact, allowing Hsp70 binding, and releasing the contact in adjacent subunits. Our data suggest a wavelike activation of ClpB subunits around the ring.

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Author details

  1. Marta Carroni

    Birkbeck College, University of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Eva Kummer

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

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

    Ludwig-Maximilians-University Munich, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Daniel K Clare

    Birkbeck College, University of London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Irmgard Sinning

    Biochemie-Zentrum der Universität Heidelberg (BZH), Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Jürgen Kopp

    Biochemie-Zentrum der Universität Heidelberg (BZH), Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Axel Mogk

    Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Bernd Bukau

    Zentrum für Molekulare Biologie der Universität Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Helen Saibil

    Birkbeck College, University of London, London, United Kingdom
    For correspondence
    h.saibil@mail.cryst.bbk.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Copyright

© 2014, Carroni et al.

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

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  1. Marta Carroni
  2. Eva Kummer
  3. Yuki Oguchi
  4. Petra Wendler
  5. Daniel K Clare
  6. Irmgard Sinning
  7. Jürgen Kopp
  8. Axel Mogk
  9. Bernd Bukau
  10. Helen Saibil
(2014)
Head-to-tail interactions of the coiled-coil domains regulate ClpB cooperation with Hsp70 in protein disaggregation
eLife 3:e02481.
https://doi.org/10.7554/eLife.02481

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https://doi.org/10.7554/eLife.02481