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 extremely valuable 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, compared to the native environment. Understanding the impact of detergents on membrane proteins is, therefore, of paramount importance to assess the biological relevance of results acquired in detergents. I will review how alkyl phosphocholines, the most widely used detergent in solution-NMR studies, impact the membrane protein structure, with an emphasis on mitochondrial carriers. I will show from a combination of experiment and theory, that while phosphocholines are often successful for membrane protein solubilization, a growing number of examples point to destabilizing and denaturing properties, notably for α-helical membrane proteins. This in-depth analysis of the physiological meaning of membrane protein structures obtained in detergents underscores the prominent role of simulations to rapidly diagnose pathological cases.

Understanding detergent-induced structural and dynamic perturbations in mitochondrial carriers

256th National Meeting (2018)

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