Molecular mechanism for the crystallization of bacteriorhodopsin in lipidic cubic phases

Crystals of transmembrane proteins may be grown from detergent solutions or in a matrix of membranous lipid bilayers existing in a liquid crystalline state and forming a cubic phase (in cubo). While crystallization in micella r solutions appears analogous to that for soluble proteins, crystallization in lipidic matrices is poorly understood. As this method was shown to be a pplicable to several membrane proteins, understanding its mechanism will fa cilitate a rational design of crystallization, minimizing the laborious scr eening of a large number of parameters. Using polarization microscopy and l ow-angle X-ray diffraction, experimental evidence is provided to support a mechanistic model for the in cubo crystallization of bacteriorhodopsin in a lipid matrix. Membrane proteins are thought to reside in curved lipid bila yers, to diffuse into patches of lower curvature and to incorporate into la ttices which associate to form highly ordered three-dimensional crystals. C ritical testing of this model is necessary to generalize it to other membra ne proteins. (C) 2001 Published by Elsevier Science BY. on behalf of the Fe deration of European Biochemical Societies.