The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces of native IMPs. Many proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each built around a central quaternary carbon atom derived from neopentyl glycol, with hydrophilic groups derived from maltose. Representatives of this maltose–neopentyl glycol (MNG) amphiphile family show favorable behavior relative to conventional detergents, as manifested in multiple membrane protein systems, leading to enhanced structural stability and successful crystallization. MNG amphiphiles are promising tools for membrane protein science because of the ease with which they may be prepared and the facility with which their structures may be varied.
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This work was supported by US National Institutes of Health (NIH) grant P01 GM75913 (S.H.G.), NS28471 (B.K.), by the Lundbeck Foundation (S.G.F.R., C.J.L. and U.G.), by the Danish National Research Council (C.J.L., U.G.), by the European Community's Seventh Framework Programme FP7/2007-2013 under grant agreement no. HEALTH-F4-2007-201924, EDICT Consortium (K.G., U.G. and B.B.) and by NIH grant GM083118 and NIH Protein Structure Initiative grants U54 GM-074901 (J.L. Markley, PI; B.G.F.) and U54 GM094584 (B.G.F.). This work was also supported by grant no. R21HL087895 from the US National Heart, Lung, and Blood Institute, by the Texas Norman Hackerman Advanced Research Program under grant no. 010674-0034-2009 (to L.G.) and by the Center for Membrane Protein Research, Texas Tech University Health Sciences Center. R.R.R. was funded by the Defence Science and Technology Laboratory. We thank P. Laible (Argonne National Laboratory, Chicago) for supplying membrane preparations from R. capsulatus. We acknowledge SOLEIL (Saint-Aubin, France) for provision of synchrotron radiation facilities, and we would like to thank B. Guimaraes for assistance in using the beamline Proxima 1. We also thank R. Kaback (University of California, Los Angeles) and G. Leblanc (Institut de Biologie et Technologies–Saclay) for the MelB expression system. M.A.G. acknowledges support from the US National Science Foundation East Asia and Pacific Summer Institutes Fellowship program. We thank G. Cecchini (University of California, San Francisco) and J. Ruprecht (Medical Research Council Mitochondrial Biology Unit, Cambridge) for the purified SQR and the details of the SQR functional assay, and we acknowledge the assistance of P. Nixon in the analysis of the SQR functional data.
P.S.C, S.G.F.R., B.K. and S.H.G. are co-inventors on a patent application that covers the MNG amphiphiles.
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Chae, P., Rasmussen, S., Rana, R. et al. Maltose–neopentyl glycol (MNG) amphiphiles for solubilization, stabilization and crystallization of membrane proteins. Nat Methods 7, 1003–1008 (2010). https://doi.org/10.1038/nmeth.1526
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