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Article Dans Une Revue Methods Année : 2020

Lactobionamide-based fluorinated detergent for functional and structural stabilization of membrane proteins

Clarisse Faugier
  • Fonction : Auteur
Sébastien Igonet
  • Fonction : Auteur
Romain Besson
  • Fonction : Auteur
Anass Jawhari
  • Fonction : Auteur correspondant

Résumé

Membrane proteins (MPs) are important drug discovery targets for a wide range of diseases. Conventional detergents such as n-Dodecyl β-D-maltoside have been used largely and efficiently to solubilize MPs with varying degrees of success concerning MPs functionality and stability. Fluorinated surfactants (FSs) have shown a great potential for the stabilization of various MPs. However, so far only a limited number of reports have demonstrated the ability of FSs to solubilize MPs from biological membranes. We report herein the use of a fluorinated lactobionamide-based detergent named FLAC6 for functional and structural stabilization of membrane proteins. We first demonstrated that FLAC6 efficiently solubilized three membrane proteins i.e. the native adenosine receptor A2AR, a G protein-coupled receptor, and two native transporters AcrB and BmrA. The resulting affinity purified MPs were highly pure, homogenous and aggregates free. Furthermore, the functionality of each MP was well maintained. Finally, striking overstabilization features were observed. Indeed, the Tm of native A2AR, AcrB and BmrA could be improved by 7, ~9 and ~ 23 °C, respectively when FLAC6 was used instead of the reference detergent. This work illustrates that FLAC6 is an efficient tool to maintain structural and functional integrities of different MPs belonging to different classes, providing a new avenue for functional stabilization of highly druggable and challenging membrane proteins involved in unmet medical needs.
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hal-03493270 , version 1 (17-10-2022)

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Clarisse Faugier, Sébastien Igonet, Damien Cornut, Romain Besson, Gregory Durand, et al.. Lactobionamide-based fluorinated detergent for functional and structural stabilization of membrane proteins. Methods, 2020, 180, pp.19 - 26. ⟨10.1016/j.ymeth.2020.02.005⟩. ⟨hal-03493270⟩
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