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

Christophe Chipot, François Dehez, Jason R. Schnell, Nicole Zitzmann, Eva Pebay-Peyroula, Laurent J. Catoire, Bruno Miroux, Edmund R.S. Kunji, Gianluigi Veglia, Timothy A. Cross, Paul Schanda

Research output: Contribution to journalReview articlepeer-review

108 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)3559-3607
Number of pages49
JournalChemical Reviews
Issue number7
StatePublished - Apr 11 2018

Bibliographical note

Funding Information:
We thank Dr. Vilius Kurauskas and Audrey Hessel for numerous discussions and for their groundbreaking work on mitochondrial carriers in DPC, which initiated this work. We thank Dr. Beate Bersch (IBS Grenoble, France), Dr. Robert Schneider (University of Lille, France), Dr. Stephanie Ravaud (IBCP Lyon, France), Dr. Karine Moncoq and Fabrice Giusti (IBPC Paris, France), and Dr. Phillip Stansfeld (University of Oxford, UK) for many insightful discussions and the three anonymous reviewers for their in-depth study of our manuscript and helpful suggestions. G.V. was supported by the National Institute of Health (GM 64742 and GM 72701). P.S. was supported by the European Research Council (ERC-StG-2012-311318). J.R.S. was supported by the UK Medical Research Council (M019152 and K018590). T.A.C. was supported in part by NIH grants AI023007 and AI-119178 and acknowledges the National High Magnetic Field Lab, supported by the NSF DMR-1157490 and the State of Florida. L.J.C. and B.M. were supported by the Centre National de la Recherche Scientifique, INSERM, by the “Initiative d’Excellence” program from the French State (Grant “DYNAMO”, ANR-11-LABEX-0011-01) and by the grant GHREDYN, ANR-13-BSV8-0006-01 from the Agence Natio-nale de la Recherche (ANR) to L.J.C. E.R.S.K. is supported by the UK Medical Research Council (MC_UU_00015/1). E.P.-P. was supported by the Institut Universitaire de France. The National High Magnetic Field Lab (NHMFL) is supported by the NSF Cooperative agreement DMR-1157490 and the State of Florida.

Publisher Copyright:
© 2018 American Chemical Society.


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