The Journal of Membrane Biology

, Volume 247, Issue 9–10, pp 965–970 | Cite as

How Amphipols Embed Membrane Proteins: Global Solvent Accessibility and Interaction with a Flexible Protein Terminus

  • Manuel Etzkorn
  • Manuela Zoonens
  • Laurent J. Catoire
  • Jean-Luc Popot
  • Sebastian HillerEmail author


Amphipathic polymers called amphipols provide a valuable alternative to detergents for keeping integral membrane proteins soluble in aqueous buffers. Here, we characterize spatial contacts of amphipol A8-35 with membrane proteins from two architectural classes: The 8-stranded β-barrel outer membrane protein OmpX and the α-helical protein bacteriorhodopsin. OmpX is well structured in A8-35, with its barrel adopting a fold closely similar to that in dihexanoylphosphocholine micelles. The accessibility of A8-35-trapped OmpX by a water-soluble paramagnetic molecule is highly similar to that in detergent micelles and resembles the accessibility in the natural membrane. For the α-helical protein bacteriorhodopsin, previously shown to keep its fold and function in amphipols, NMR data show that the imidazole protons of a polyhistidine tag at the N-terminus of the protein are exchange protected in the presence of detergent and lipid bilayer nanodiscs, but not in amphipols, indicating the absence of an interaction in the latter case. Overall, A8-35 exhibits protein interaction properties somewhat different from detergents and lipid bilayer nanodiscs, while maintaining the structure of solubilized integral membrane proteins.


NMR spectroscopy Membrane proteins Paramagnetic surface mapping OmpX Bacteriorhodopsin 



Polyacrylate-based amphipol, carrying ~25 % octylamide chains, ~40 % isopropyl-amide ones, and ~35 % free carboxylates












A gadolinium ion chelated with 1,4,7,10-tetraazocyclododecane-N,N′,N″,N′″-tetraacetic acid


Outer membrane protein X



We thank Profs. Kurt Wüthrich and Gerhard Wagner for their kind support of materials and instrument time, Prof. Gerhard Wider for helpful discussions and F. Giusti (UMR 7099) for the synthesis of deuterated A8-35. This work was supported by grants from the German Academic Exchange Service (DAAD) and the DFG (ET 103/2-1) to M.E., as well as the Swiss National Science Foundation (Grant PP00P3_128419) and the European Research Council (FP7 contract MOMP 281764) to S.H., by the French Centre National de la Recherche Scientifique, Université Paris-7, and grants from the CNRS interdisciplinary program Physique et Chimie du Vivant, from the EU (BIO4-CT98-0269), from the Human Frontier Science Program Organization (Grant RG00223/2000-M), and from E.U. Specific Targeted Research Project IMPS (Innovative tools for membrane protein structural proteomics) to J.L.P.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Manuel Etzkorn
    • 1
  • Manuela Zoonens
    • 2
  • Laurent J. Catoire
    • 2
  • Jean-Luc Popot
    • 2
  • Sebastian Hiller
    • 3
    Email author
  1. 1.Institute of Physical BiologyHeinrich Heine UniversityDüsseldorfGermany
  2. 2.UMR 7099, Institut de BiologiePhysico-ChimiqueCNRS/Université Paris-7ParisFrance
  3. 3.Biozentrum, University of BaselBaselSwitzerland

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