Nature Biotechnology
21, 171 - 176 (2003)
Published online: 13 January 2003; | doi:10.1038/nbt776
Lipopeptide detergents designed for the structural study of membrane proteinsClare-Louise McGregor1, Lu Chen2, Neil C. Pomroy2, Peter Hwang3, Sandy Go2, Avijit Chakrabartty1, 2, 3
& Gilbert G. Privé1, 2, 31
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada M5G 2M9. 2
Division of Molecular and Structural Biology, Ontario Cancer Institute, University Health Network, 610 University Avenue, Toronto, ON, Canada M5G 2M9. 3
Department of Biochemistry, University of Toronto, Toronto, ON, Canada M5S 1A8.
Correspondence should be addressed to Gilbert G. Privé prive@uhnres.utoronto.caThe structural study of membrane proteins requires detergents that can effectively mimic lipid bilayers, and the choice of detergent is often a compromise between detergents that promote protein stability and detergents that form small micelles. We describe lipopeptide detergents (LPDs), a new class of amphiphile consisting of a peptide scaffold that supports two alkyl chains, one anchored to each end of an  -helix. The goal was to design a molecule that could self-assemble into a cylindrical micelle with a rigid outer hydrophilic shell surrounding an inner lipidic core. Consistent with this design, LPDs self-assemble into small micelles, can disperse phospholipid membranes, and are gentle, nondenaturing detergents that preserve the structure of the membrane proteins in solution for extended periods of time. The LPD design allows for a membrane-like packing of the alkyl chains in the core of the molecular assemblies, possibly explaining their superior properties relative to traditional detergents in stabilizing membrane protein structures.
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