1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation

  1. Bence Hajdusits
  2. Marcin J Suskiewicz
  3. Nikolas Hundt
  4. Anton Meinhart
  5. Robert Kurzbauer
  6. Julia Leodolter
  7. Philipp Kukura  Is a corresponding author
  8. Tim Clausen  Is a corresponding author
  1. Research Institute of Molecular Pathology, Austria
  2. University of Oxford, United Kingdom
  3. Ludwig Maximilian University of Munich, Germany
Research Article
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Cite this article as: eLife 2021;10:e63505 doi: 10.7554/eLife.63505

Abstract

In Gram-positive bacteria, the McsB protein arginine kinase is central to protein quality control, labelling aberrant molecules for degradation by the ClpCP protease. Despite its importance for stress response and pathogenicity, it is still elusive how the bacterial degradation labelling is regulated. Here, we delineate the mechanism how McsB targets aberrant proteins during stress conditions. Structural data reveal a self-compartmentalized kinase, in which the active sites are sequestered in a molecular cage. The 'closed' octamer interconverts with other oligomers in a phosphorylation-dependent manner and, contrary to these 'open' forms, preferentially labels unfolded proteins. In vivo data show that heat-shock triggers accumulation of higher-order oligomers, of which the octameric McsB is essential for surviving stress situations. The interconversion of open and closed oligomers represents a distinct regulatory mechanism of a degradation labeler, allowing the McsB kinase to adapt its potentially dangerous enzyme function to the needs of the bacterial cell.

Data availability

Structure factor amplitudes and Coordinate files have been deposited in the Protein Data Bank under the accession number 6TV6.

Article and author information

Author details

  1. Bence Hajdusits

    Structural Biology, Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  2. Marcin J Suskiewicz

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Nikolas Hundt

    Department of Cellular Physiology, Ludwig Maximilian University of Munich, Planegg-Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8217-671X
  4. Anton Meinhart

    Structural Biology, Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert Kurzbauer

    Structural Biology, Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  6. Julia Leodolter

    Structural Biology, Research Institute of Molecular Pathology, Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Philipp Kukura

    Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    philipp.kukura@chem.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  8. Tim Clausen

    Structural Biology, Research Institute of Molecular Pathology, Vienna, Austria
    For correspondence
    tim.clausen@imp.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1582-6924

Funding

H2020 European Research Council (AdG 694978)

  • Tim Clausen

FFG (Headquarter Grant 852936)

  • Tim Clausen

H2020 European Research Council (CoG 819593)

  • Philipp Kukura

Deutsche Forschungsgemeinschaft (Return Grant HU 2462/3-1)

  • Nikolas Hundt

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. William I Weis, Stanford University School of Medicine, United States

Publication history

  1. Preprint posted: September 8, 2020 (view preprint)
  2. Received: September 27, 2020
  3. Accepted: July 29, 2021
  4. Accepted Manuscript published: July 30, 2021 (version 1)
  5. Version of Record published: August 17, 2021 (version 2)

Copyright

© 2021, Hajdusits 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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