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Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations

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 SAN...

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Autores principales: Bengtsen, Tone, Holm, Viktor L, Kjølbye, Lisbeth Ravnkilde, Midtgaard, Søren R, Johansen, Nicolai Tidemand, Tesei, Giulio, Bottaro, Sandro, Schiøtt, Birgit, Arleth, Lise, Lindorff-Larsen, Kresten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426092/
https://www.ncbi.nlm.nih.gov/pubmed/32729831
http://dx.doi.org/10.7554/eLife.56518
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author Bengtsen, Tone
Holm, Viktor L
Kjølbye, Lisbeth Ravnkilde
Midtgaard, Søren R
Johansen, Nicolai Tidemand
Tesei, Giulio
Bottaro, Sandro
Schiøtt, Birgit
Arleth, Lise
Lindorff-Larsen, Kresten
author_facet Bengtsen, Tone
Holm, Viktor L
Kjølbye, Lisbeth Ravnkilde
Midtgaard, Søren R
Johansen, Nicolai Tidemand
Tesei, Giulio
Bottaro, Sandro
Schiøtt, Birgit
Arleth, Lise
Lindorff-Larsen, Kresten
author_sort Bengtsen, Tone
collection PubMed
description 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 pave the way for future integrative studies of larger complex systems such as membrane proteins embedded in nanodiscs.
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spelling pubmed-74260922020-08-17 Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations Bengtsen, Tone Holm, Viktor L Kjølbye, Lisbeth Ravnkilde Midtgaard, Søren R Johansen, Nicolai Tidemand Tesei, Giulio Bottaro, Sandro Schiøtt, Birgit Arleth, Lise Lindorff-Larsen, Kresten eLife Structural Biology and Molecular Biophysics 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 pave the way for future integrative studies of larger complex systems such as membrane proteins embedded in nanodiscs. eLife Sciences Publications, Ltd 2020-07-30 /pmc/articles/PMC7426092/ /pubmed/32729831 http://dx.doi.org/10.7554/eLife.56518 Text en © 2020, Bengtsen et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Structural Biology and Molecular Biophysics
Bengtsen, Tone
Holm, Viktor L
Kjølbye, Lisbeth Ravnkilde
Midtgaard, Søren R
Johansen, Nicolai Tidemand
Tesei, Giulio
Bottaro, Sandro
Schiøtt, Birgit
Arleth, Lise
Lindorff-Larsen, Kresten
Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
title Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
title_full Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
title_fullStr Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
title_full_unstemmed Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
title_short Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
title_sort structure and dynamics of a nanodisc by integrating nmr, saxs and sans experiments with molecular dynamics simulations
topic Structural Biology and Molecular Biophysics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426092/
https://www.ncbi.nlm.nih.gov/pubmed/32729831
http://dx.doi.org/10.7554/eLife.56518
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