Architecture of the human mTORC2 core complex

  1. Edward Stuttfeld
  2. Christopher H S Aylett
  3. Stefan Imseng
  4. Daniel Boehringer
  5. Alain Scaiola
  6. Evelyn Sauer
  7. Michael N Hall  Is a corresponding author
  8. Timm Maier  Is a corresponding author
  9. Nenad Ban  Is a corresponding author
  1. University of Basel, Switzerland
  2. ETH Zürich, Switzerland

Abstract

The mammalian target of rapamycin (mTOR) is a key protein kinase controlling cellular metabolism and growth. It is part of the two structurally and functionally distinct multiprotein complexes mTORC1 and mTORC2. Dysregulation of mTOR occurs in diabetes, cancer and neurological disease. We report the architecture of human mTORC2 at intermediate resolution, revealing a conserved binding site for accessory proteins on mTOR and explaining the structural basis for the rapamycin insensitivity of the complex.

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The following data sets were generated

Article and author information

Author details

  1. Edward Stuttfeld

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3932-9076
  2. Christopher H S Aylett

    Institute for Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Stefan Imseng

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Boehringer

    Institute for Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Alain Scaiola

    Institute for Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Evelyn Sauer

    Biozentrum, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Michael N Hall

    Biozentrum, University of Basel, Basel, Switzerland
    For correspondence
    m.hall@unibas.ch
    Competing interests
    The authors declare that no competing interests exist.
  8. Timm Maier

    Biozentrum, University of Basel, Basel, Switzerland
    For correspondence
    timm.maier@unibas.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7459-1363
  9. Nenad Ban

    Institute for Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland
    For correspondence
    ban@mol.biol.ethz.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9527-210X

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (51NF40_141735_NCCR)

  • Nenad Ban

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030_159492)

  • Michael N Hall

European Research Council (609883)

  • Michael N Hall

Sir Henry Dale Fellowship (206212/Z/17/Z)

  • Christopher H S Aylett

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (138262)

  • Nenad Ban

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (159696)

  • Timm Maier

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030B_163478)

  • Nenad Ban

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

Reviewing Editor

  1. Nahum Sonenberg, McGill University, Canada

Publication history

  1. Received: October 25, 2017
  2. Accepted: February 8, 2018
  3. Accepted Manuscript published: February 9, 2018 (version 1)
  4. Version of Record published: March 5, 2018 (version 2)

Copyright

© 2018, Stuttfeld 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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  1. Edward Stuttfeld
  2. Christopher H S Aylett
  3. Stefan Imseng
  4. Daniel Boehringer
  5. Alain Scaiola
  6. Evelyn Sauer
  7. Michael N Hall
  8. Timm Maier
  9. Nenad Ban
(2018)
Architecture of the human mTORC2 core complex
eLife 7:e33101.
https://doi.org/10.7554/eLife.33101
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