Lipidic Cubic Phases: New Matrices for the Three-Dimensional Crystallization of Membrane Proteins

The major constraint in attaining high resolution structures of membrane proteins by X-ray crystallography is the growth of well-ordered three-dimensional crystals. To enable such crystallizations, we have used lipidic cubic phases consisting of monoglycerides and water. Bacteriorhodopsin and lysozyme, as paradigms of membrane and soluble proteins, nucleate and grow to well-ordered crystals that diffract X-rays isotropically in all three dimensions to 2.0 Å. We envisage bacteriorhodopsin to partition into, and diffuse within, the bilayer of a lipidic cubic matrix, while the polar lysozyme resides in the aqueous compartment thereof. The phenomenology of bicontinuous cubic phases, consisting of curved bilayers whose structures follow infinitely periodic minimal surfaces (IPMS), is presented. Detailed prescriptions of the preparation of lipidic cubic phase matrices are given and their potential for the crystallization of other biological macromolecules is discussed. Copyright 1998 Academic Press.