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

TitlePerturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.
Publication TypeJournal Article
Year of Publication2018
AuthorsChipot, C, Dehez, F, Schnell, JR, Zitzmann, N, Pebay-Peyroula, E, Catoire, LJ, Miroux, B, Kunji, ERS, Veglia, G, Cross, TA, Schanda, P
JournalChem Rev
Volume118
Issue7
Pagination3559-3607
Date Published2018 Apr 11
ISSN1520-6890
Abstract

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.

DOI10.1021/acs.chemrev.7b00570
Alternate JournalChem. Rev.
Citation Key10.1021/acs.chemrev.7b00570
PubMed ID29488756
PubMed Central IDPMC5896743
Grant List311318 / / European Research Council / International
MR/K018590/1 / / Medical Research Council / United Kingdom
MC_U105663139 / / Medical Research Council / United Kingdom
R01 GM064742 / GM / NIGMS NIH HHS / United States
R01 AI023007 / AI / NIAID NIH HHS / United States