Styrene-Maleic Acid Copolymer Nanodiscs to Determine the Shape of Membrane Proteins

Cheol Jeong, Ryan Franklin, Karen J Edler, Kenno Vanommeslaeghe, Susan Krueger, Joseph E Curtis

Research output: Contribution to journalArticle

Abstract

Lipid nanodiscs can be used to solubilize functional membrane proteins (MPs) in nativelike environments. Thus, they are promising reagents that have been proven useful to characterize MPs. Both protein and non-protein molecular belts have shown promise to maintain the structural integrity of MPs in lipid nanodiscs. Small-angle neutron scattering (SANS) can be used to determine low-resolution structures of proteins in solution, which can be enhanced through the use of contrast variation methods. We present theoretical contrast variation SANS results for protein and styrene-maleic acid copolymer (SMA) belt 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) nanodiscs with and without additional bound or transmembrane proteins. The predicted scattering properties are derived from atomistic molecular dynamics simulations to account for conformational fluctuations, and we determine deuterium-labeling conditions such that SANS intensity profiles only include contributions from the scattering of the MP of interest. We propose strategies to tune the neutron scattering length densities (SLDs) of the SMA and DMPC using selective deuterium labeling such that the SLD of the nanodisc becomes homogeneous and its scattering can essentially be eliminated in solvents containing an appropriate amount of D2O. These finely tuned labeled polymer-based nanodiscs are expected to be useful to extract the size and molecular shape information of MPs using SANS-based contrast variation experiments, and they can be used with MPs of any molecular weight.

Original languageEnglish
Pages (from-to)1034-1044
Number of pages11
JournalJournal of Physical Chemistry B
Volume126
Issue number5
DOIs
Publication statusPublished - 10 Feb 2022

Keywords

  • Lipid Bilayers/chemistry
  • Maleates/chemistry
  • Membrane Proteins/chemistry
  • Nanostructures/chemistry
  • Scattering, Small Angle

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