1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics

Large protein organelles form a new iron sequestration system with high storage capacity

  1. Tobias W Giessen  Is a corresponding author
  2. Benjamin J Orlando
  3. Andrew A Verdegaal
  4. Melissa G Chambers
  5. Jules Gardener
  6. David C Bell
  7. Gabriel Birrane
  8. Maofu Liao  Is a corresponding author
  9. Pamela A Silver  Is a corresponding author
  1. Harvard Medical School, United States
  2. Harvard University, United States
https://doi.org/10.7554/eLife.46070
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Cite this article
  1. Tobias W Giessen
  2. Benjamin J Orlando
  3. Andrew A Verdegaal
  4. Melissa G Chambers
  5. Jules Gardener
  6. David C Bell
  7. Gabriel Birrane
  8. Maofu Liao
  9. Pamela A Silver
(2019)
Large protein organelles form a new iron sequestration system with high storage capacity
eLife 8:e46070.
https://doi.org/10.7554/eLife.46070
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Abstract

Iron storage proteins are essential for cellular iron homeostasis and redox balance. Ferritin proteins are the major storage units for bioavailable forms of iron. Some organisms lack ferritins, and it is not known how they store iron. Encapsulins, a class of protein-based organelles, have recently been implicated in microbial iron and redox metabolism. Here, we report the structural and mechanistic characterization of a 42 nm two-component encapsulin-based iron storage compartment from Quasibacillus thermotolerans. Using cryo-electron microscopy and x-ray crystallography, we reveal the assembly principles of a thermostable T = 4 shell topology and its catalytic ferroxidase cargo and show interactions underlying cargo-shell co-assembly. This compartment has an exceptionally large iron storage capacity storing over 23,000 iron atoms. Our results reveal a new approach for survival in diverse habitats with limited or fluctuating iron availability via an iron storage system able to store 10 to 20 times more iron than ferritin.

Data availability

A cryo-EM density map of the cargo-loaded IMEF encapsulin has been deposited in the Electron Microscopy Data Bank under the accession number 9383. The corresponding atomic coordinates for the atomic model have been deposited in the Protein Data Bank (accession number: 6NJ8). Atomic coordinates for the IMEF cargo protein have been deposited in the Protein Data Bank under accession number 6N63.

The following data sets were generated

Article and author information

Author details

  1. Tobias W Giessen

    Department of Systems Biology, Harvard Medical School, Boston, United States
    For correspondence
    tgiessen@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6328-2031

  2. Benjamin J Orlando

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Andrew A Verdegaal

    Department of Systems Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4517-6961

  4. Melissa G Chambers

    Department of Cell Biology, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5111-7194

  5. Jules Gardener

    Center for Nanoscale Systems, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. David C Bell

    Center for Nanoscale Systems, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Gabriel Birrane

    Department of Medicine, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1759-5499

  8. Maofu Liao

    Department of Cell Biology, Harvard Medical School, Boston, United States
    For correspondence
    maofu_liao@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

  9. Pamela A Silver

    Department of Systems Biology, Harvard Medical School, Boston, United States
    For correspondence
    pamela_silver@hms.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

German National Academy of Sciences Leopoldina (LPDS 2014-05)

  • Tobias W Giessen

Gordon and Betty Moore Foundation (5506)

  • Tobias W Giessen
  • Pamela A Silver

Wyss Institute for Biologically Inspired Engineering

  • Tobias W Giessen
  • Pamela A Silver

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

Reviewing Editor

  1. Werner Kühlbrandt, Max Planck Institute of Biophysics, Germany

Version history

  1. Received: February 13, 2019
  2. Accepted: July 6, 2019
  3. Accepted Manuscript published: July 8, 2019 (version 1)
  4. Version of Record published: July 31, 2019 (version 2)

Copyright

© 2019, Giessen 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. Tobias W Giessen
  2. Benjamin J Orlando
  3. Andrew A Verdegaal
  4. Melissa G Chambers
  5. Jules Gardener
  6. David C Bell
  7. Gabriel Birrane
  8. Maofu Liao
  9. Pamela A Silver
(2019)
Large protein organelles form a new iron sequestration system with high storage capacity
eLife 8:e46070.
https://doi.org/10.7554/eLife.46070

Share this article

https://doi.org/10.7554/eLife.46070

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