Structure and dynamics of a nanodisc by integrating NMR, SAXS and SANS experiments with molecular dynamics simulations
- University of Copenhagen, Denmark
- Aarhus University, Denmark
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
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The 3D solution structure of discoidal high-density lipoprotein particlesRCSB Protein Data Bank, 2N5E.
Article and author information
Author details
Kresten Lindorff-Larsen
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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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
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The protein dynamical transition at ~200 K, where the biomolecule transforms from a harmonic, non-functional form to an anharmonic, functional state, has been thought to be slaved to the thermal activation of dynamics in its surface hydration water. Here, by selectively probing the dynamics of protein and hydration water using elastic neutron scattering and isotopic labeling, we found that the onset of anharmonicity in the two components around 200 K is decoupled. The one in protein is an intrinsic transition, whose characteristic temperature is independent of the instrumental resolution time, but varies with the biomolecular structure and the amount of hydration, while the one of water is merely a resolution effect.
