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

Tone Bengtsen; Viktor L Holm; Lisbeth Ravnkilde Kjølbye; Søren R Midtgaard; Nicolai Tidemand Johansen; Giulio Tesei; Sandro Bottaro; Birgit Schiøtt; Lise Arleth; Kresten Lindorff-Larsen

doi:10.7554/eLife.56518

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

Elife. 2020 Jul 30:9:e56518. doi: 10.7554/eLife.56518.

Affiliations

¹ Structural Biology and NMR Laboratory and Linderstrøm-Lang Centre for Protein Science, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
² Structural Biophysics, X-ray and Neutron Science, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
³ Department of Chemistry, Aarhus University, Aarhus, Denmark.
⁴ Novo Nordisk A/S, Måløv, 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 pave the way for future integrative studies of larger complex systems such as membrane proteins embedded in nanodiscs.

Keywords: E. coli; NMR; SANS; SAXS; lipids; membrane structure; molecular biophysics; molecular simulations; structural biology.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Lipid Bilayers / chemistry
Magnetic Resonance Spectroscopy*
Membrane Proteins / chemistry
Molecular Dynamics Simulation
Nanostructures / ultrastructure*
Neutron Diffraction*
Scattering, Small Angle*
X-Ray Diffraction*

Substances

Lipid Bilayers
Membrane Proteins

Grants and funding

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