Styrene-Maleic Acid Copolymer Nanodiscs to Determine the Shape of Membrane Proteins
Jeong, Cheol ; Franklin, Ryan ; Edler, Karen J. LU
; Vanommeslaeghe, Kenno
; Krueger, Susan
and Curtis, Joseph E.
(2022)
In Journal of Physical Chemistry B
126(5).
p.1034-1044
- 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... (More)
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.
(Less)
- author
- Jeong, Cheol
; Franklin, Ryan
; Edler, Karen J.
LU
; Vanommeslaeghe, Kenno
; Krueger, Susan
and Curtis, Joseph E.
- publishing date
- 2022-02-10
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Physical Chemistry B
- volume
- 126
- issue
- 5
- pages
- 11 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:35089036
- scopus:85124032849
- ISSN
- 1520-6106
- DOI
- 10.1021/acs.jpcb.1c05050
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © 2022 American Chemical Society
- id
- 51ed4d5f-65de-4582-a9da-e156a96ec3e1
- date added to LUP
- 2022-07-12 14:00:30
- date last changed
- 2024-04-16 09:45:48
@article{51ed4d5f-65de-4582-a9da-e156a96ec3e1,
abstract = {{<p>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 D<sub>2</sub>O. 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.</p>}},
author = {{Jeong, Cheol and Franklin, Ryan and Edler, Karen J. and Vanommeslaeghe, Kenno and Krueger, Susan and Curtis, Joseph E.}},
issn = {{1520-6106}},
language = {{eng}},
month = {{02}},
number = {{5}},
pages = {{1034--1044}},
publisher = {{The American Chemical Society (ACS)}},
series = {{Journal of Physical Chemistry B}},
title = {{Styrene-Maleic Acid Copolymer Nanodiscs to Determine the Shape of Membrane Proteins}},
url = {{http://dx.doi.org/10.1021/acs.jpcb.1c05050}},
doi = {{10.1021/acs.jpcb.1c05050}},
volume = {{126}},
year = {{2022}},
}