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Chem Rev. 2018 Apr 11;118(7):3559-3607. doi: 10.1021/acs.chemrev.7b00570. Epub 2018 Feb 28.

Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.

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SRSMC , UMR 7019 Université de Lorraine CNRS , Vandoeuvre-les-Nancy F-54500 , France.
Laboratoire International Associé CNRS and University of Illinois at Urbana-Champaign , Vandoeuvre-les-Nancy F-54506 , France.
Department of Physics , University of Illinois at Urbana-Champaign , 1110 West Green Street , Urbana , Illinois 61801 , United States.
Department of Biochemistry , University of Oxford , South Parks Road , Oxford OX1 3QU , United Kingdom.
Université Grenoble Alpes, CEA, CNRS, IBS , Grenoble F-38000 , France.
Laboratory of Biology and Physico-Chemistry of Membrane Proteins , Institut de Biologie Physico-Chimique (IBPC), UMR 7099 CNRS , Paris 75005 , France.
University Paris Diderot , Paris 75005 , France.
PSL Research University , Paris 75005 , France.
Medical Research Council Mitochondrial Biology Unit , University of Cambridge , Cambridge CB2 0XY , United Kingdom.
Department of Biochemistry, Molecular Biology, and Biophysics, and Department of Chemistry , University of Minnesota , Minneapolis , Minnesota 55455 , United States.
National High Magnetic Field Laboratory , Florida State University , Tallahassee , Florida 32310 , United States.


Membrane proteins perform a host of vital cellular functions. Deciphering the molecular mechanisms whereby they fulfill these functions requires detailed biophysical and structural investigations. Detergents have proven pivotal to extract the protein from its native surroundings. Yet, they provide a milieu that departs significantly from that of the biological membrane, to the extent that the structure, the dynamics, and the interactions of membrane proteins in detergents may considerably vary, as compared to the native environment. Understanding the impact of detergents on membrane proteins is, therefore, crucial to assess the biological relevance of results obtained in detergents. Here, we review the strengths and weaknesses of alkyl phosphocholines (or foscholines), the most widely used detergent in solution-NMR studies of membrane proteins. While this class of detergents is often successful for membrane protein solubilization, a growing list of examples points to destabilizing and denaturing properties, in particular for α-helical membrane proteins. Our comprehensive analysis stresses the importance of stringent controls when working with this class of detergents and when analyzing the structure and dynamics of membrane proteins in alkyl phosphocholine detergents.

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