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

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Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.
Chemical Reviews ( IF 51.4 ) Pub Date : 2018-02-28 , DOI: 10.1021/acs.chemrev.7b00570
Christophe Chipot _{1,

2,

3} , François Dehez _{1,

2} , Jason R Schnell ₄ , Nicole Zitzmann ₄ , Eva Pebay-Peyroula ₅ , Laurent J Catoire _{6,

7,

8} , Bruno Miroux _{6,

7,

8} , Edmund R S Kunji ₉ , Gianluigi Veglia ₁₀ , Timothy A Cross ₁₁ , Paul Schanda ₅

Affiliation

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.

中文翻译：

烷基磷酸胆碱洗涤剂中天然膜蛋白结构的扰动：核磁共振和生物物理研究的批判性评估。

膜蛋白执行许多重要的细胞功能。破译它们实现这些功能的分子机制需要详细的生物物理和结构研究。事实证明，洗涤剂对于从天然环境中提取蛋白质至关重要。然而，它们提供的环境与生物膜的环境显着不同，以至于与天然环境相比，去垢剂中膜蛋白的结构、动力学和相互作用可能有很大差异。因此，了解去垢剂对膜蛋白的影响对于评估去垢剂中获得的结果的生物学相关性至关重要。在这里，我们回顾了烷基磷酸胆碱（或磷胆碱）的优点和缺点，烷基磷酸胆碱是膜蛋白溶液核磁共振研究中使用最广泛的去污剂。虽然这类去污剂通常能成功溶解膜蛋白，但越来越多的例子表明其具有不稳定和变性特性，特别是对于 α-螺旋膜蛋白。我们的综合分析强调了在使用此类去污剂以及分析烷基磷酸胆碱去污剂中膜蛋白的结构和动力学时严格控制的重要性。

更新日期：2018-02-28

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