Isotropic solutions of phospholipid bicelles: a new membrane mimetic for high-resolution NMR studies of polypeptides

In order to illustrate the utility of phospholipid bicelles [Sanders, C.R. and Schwonek, J.P. (1992) Biochemistry, 31, 8898-8905] as a membrane mimetic for high-resolution NMR studies, we have recorded two-dimensional 1H NMR spectra of the tetradecameric peptide mastoparan Vespula lewisii in an isotropic aqueous solution of dimyristoyl and dihexanoyl phosphatidylcholine. Mastoparan is largely unstructured in water, but assumes a well-defined helical conformation in association with the bilayers. A pronounced periodicity of the sequential NH chemical shifts provides strong evidence that the helix axis of this short peptide is parallel, rather than perpendicular, to the bilayer plane. The bicellar solutions still require in-depth morphological characterization, but they appear to be ideal media for NMR determination of the mode of binding and the structure of membrane-associated peptides and proteins.