1. Structural Biology and Molecular Biophysics
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Structure of the human BBSome core complex

  1. Björn Udo Klink
  2. Christos Gatsogiannis
  3. Oliver Hofnagel
  4. Alfred Wittinghofer
  5. Stefan Raunser  Is a corresponding author
  1. Max Planck Institute of Molecular Physiology, Germany
Research Article
  • Cited 15
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Cite this article as: eLife 2020;9:e53910 doi: 10.7554/eLife.53910

Abstract

The BBSome is a heterooctameric protein complex that plays a central role in primary cilia homeostasis. Its malfunction causes the severe ciliopathy Bardet-Biedl syndrome (BBS). The complex acts as a cargo adapter that recognizes signaling proteins such as GPCRs and links them to the intraflagellar transport machinery. The underlying mechanism is poorly understood. Here we present a high-resolution cryo-EM structure of a human heterohexameric core subcomplex of the BBSome. The structure reveals the architecture of the complex in atomic detail. It explains how the subunits interact with each other and how disease-causing mutations hamper this interaction. The complex adopts a conformation that is open for binding to membrane-associated GTPase Arl6 and a large positively charged patch likely strengthens the interaction with the membrane. A prominent negatively charged cleft at the center of the complex is likely involved in binding of positively charged signaling sequences of cargo proteins.

Data availability

The electron density maps have been deposited to the EMDB under the accession codes EMD-10617 and EMD-10618. The final models of the BBSome were submitted to the Protein Data Bank under the accession codes 6XT9 (subunits BBS1,4,8,9,18) and 6XTB (subunits BBS1,4,5,8,9,18).

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Article and author information

Author details

  1. Björn Udo Klink

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0946-4456
  2. Christos Gatsogiannis

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4922-4545
  3. Oliver Hofnagel

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Alfred Wittinghofer

    Structural Biology Group, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5800-0236
  5. Stefan Raunser

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    stefan.raunser@mpi-dortmund.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9373-3016

Funding

Max-Planck-Gesellschaft

  • Stefan Raunser

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

Reviewing Editor

  1. Andrew P Carter, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Received: November 25, 2019
  2. Accepted: January 15, 2020
  3. Accepted Manuscript published: January 17, 2020 (version 1)
  4. Version of Record published: February 13, 2020 (version 2)

Copyright

© 2020, Klink 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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Further reading

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