Abstract

Nanodiscs are membrane mimetics that consist of a protein belt surrounding a lipid bilayer, and are broadly used for characterization of membrane proteins. Here, we investigate the structure, dynamics and biophysical properties of two small nanodiscs, MSP1D1ΔH5 and ΔH4H5. We combine our SAXS and SANS experiments with molecular dynamics simulations and previously obtained NMR and EPR data to derive and validate a conformational ensemble that represents the structure and dynamics of the nanodisc. We find that it displays conformational heterogeneity with various elliptical shapes, and with substantial differences in lipid ordering in the centre and rim of the discs. Together, our results reconcile previous apparently conflicting observations about the shape of nanodiscs, and paves the way for future integrative studies of larger complex systems such as membrane proteins embedded in nanodiscs.

Data availability

Scattering data, molecular simulations and results from reweighting are available at https://github.com/KULL-Centre/papers/tree/master/2020/nanodisc-bengtsen-et-al

The following previously published data sets were used

Article and author information

Author details

  1. Tone Bengtsen

    Department of Biology, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  2. Viktor L Holm

    Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  3. Lisbeth Ravnkilde Kjølbye

    Department of Chemistry, Aarhus University, Aarhus C, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  4. Søren R Midtgaard

    Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  5. Nicolai Tidemand Johansen

    Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  6. Giulio Tesei

    Department of Biology, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  7. Sandro Bottaro

    Department of Biology, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1606-890X
  8. Birgit Schiøtt

    Department of Chemistry, Aarhus University, Aarhus C, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  9. Lise Arleth

    Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
    For correspondence
    arleth@nbi.ku.dk
    Competing interests
    The authors declare that no competing interests exist.
  10. Kresten Lindorff-Larsen

    Department of Biology, University of Copenhagen, Copenhagen, Denmark
    For correspondence
    lindorff@bio.ku.dk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4750-6039

Funding

Danish Council for Independent Researtch

  • Birgit Schiøtt

Lundbeckfonden (BRAINSTRUC)

  • Lise Arleth
  • Kresten Lindorff-Larsen

Novo Nordisk Foundation (Hallas-Møller Stipend)

  • Kresten Lindorff-Larsen

Villum Fonden (Block grant)

  • Sandro Bottaro
  • Kresten Lindorff-Larsen

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

Copyright

© 2020, Bengtsen 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. Tone Bengtsen
  2. Viktor L Holm
  3. Lisbeth Ravnkilde Kjølbye
  4. Søren R Midtgaard
  5. Nicolai Tidemand Johansen
  6. Giulio Tesei
  7. Sandro Bottaro
  8. Birgit Schiøtt
  9. Lise Arleth
  10. Kresten Lindorff-Larsen
(2020)
Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
eLife 9:e56518.
https://doi.org/10.7554/eLife.56518

Share this article

https://doi.org/10.7554/eLife.56518

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