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The Use of Amphipols for Solution NMR Studies of Membrane Proteins: Advantages and Constraints as Compared to Other Solubilizing Media


Solution-state nuclear magnetic resonance studies of membrane proteins are facilitated by the increased stability that trapping with amphipols confers to most of them as compared to detergent solutions. They have yielded information on the state of folding of the proteins, their areas of contact with the polymer, their dynamics, water accessibility, and the structure of protein-bound ligands. They benefit from the diversification of amphipol chemical structures and the availability of deuterated amphipols. The advantages and constraints of working with amphipols are discussed and compared to those associated with other non-conventional environments, such as bicelles and nanodiscs.

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Polyacrylate-based amphipol A8-35


Low-affinity leukotriene receptor



C8E4 :



Cell-free expression


Cross-correlated relaxation-enhanced polarization transfer




A8-35 with perdeuterated octyl and isopropyl chains and a hydrogenated polyacrylate backbone






G protein-coupled receptor


12S-Hydroxyheptadeca-5Z,8E,10E-trienoic acid


Hetero-nuclear Overhauser spectroscopy


12S-Hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid


Hetero-single quantum correlation experiment


Outer membrane protein A from Klebsiella pneumoniae

LTB4 :

Leukotriene B4


Molecular dynamics


Membrane protein


Molecular weight


Non-ionic amphipol


Maltose neopentyl glycol


Nuclear magnetic resonance


Nuclear Overhauser effect




Outer membrane protein A from Escherichia coli


Outer membrane protein X from Escherichia coli


Perdeuterated A8-35


Phosphocholine amphipol

R S :

Stokes radius


Sulfonated amphipol


Sodium dodecylsulfate


Solid-state NMR


Size exclusion chromatography


Transmembrane domain of OmpA


Transverse relaxation optimized spectroscopy


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We are extremely grateful to Sophie Walmé and Marie-Noëlle Rager (ChimieParisTech, Paris), and Carine van Heijenoort (ICSN, Gif/Yvette) for assistance with NMR experiments. We express our gratitude to B. Pucci (Université d’Avignon et des Pays de Vaucluse) for his long-term involvement in the development of non-ionic amphipols. This work was supported by the Centre National de la Recherche Scientifique (CNRS), Paris-7 University (Sorbonne Paris Cité), the “Initiative d’Excellence” program from the French State (Grant “DYNAMO,” ANR-11-LABX-0011-01), Human Frontier Science Program Organization Grant RG00223/2000-M, from the Agence Nationale pour la Recherche ANR-07-BLAN-0092 “Amphipol-assisted folding of GPCRs,” and E.U. Specific Targeted Research Project “Innovative tools for membrane protein structural proteomics.” LJC is a recipient of Projects Exploratoires/Premier Soutien (PEPS, LeukomotiVe project) from the CNRS.

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Planchard, N., Point, É., Dahmane, T. et al. The Use of Amphipols for Solution NMR Studies of Membrane Proteins: Advantages and Constraints as Compared to Other Solubilizing Media. J Membrane Biol 247, 827–842 (2014).

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  • Membrane proteins
  • Solution NMR
  • Amphipols