Tables for
Volume F
Crystallography of biological macromolecules
Edited by E. Arnold, D. M. Himmel and M. G. Rossmann

International Tables for Crystallography (2012). Vol. F, ch. 4.2, p. 126   | 1 | 2 |

Section 4.2.6. Membrane-protein crystallization using cubic bicontinuous lipidic phases

H. Michela*

aMax-Planck-Institut für Biophysik, Heinrich-Hoffmann-Strasse 7, D-60528 Frankfurt/Main, Germany
Correspondence e-mail:

4.2.6. Membrane-protein crystallization using cubic bicontinuous lipidic phases

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Landau & Rosenbusch (1996[link]) introduced the use of bicontinuous cubic phases of lipids for membrane-protein crystallization. In such phases, the lipid forms a single, curved, continuous three-dimensional bilayer [see Lindblom & Rilfors (1989[link]) for a review]. One can incorporate membrane proteins into such a bilayer, as demonstrated with octyl-β-D-glucopyranoside-solubilized monomeric bacteriorhodopsin. The three-dimensional bilayer network serves as a matrix for crystallization. The membrane protein can diffuse through the bilayer, but is also able to establish polar contacts in the third dimension. Landau & Rosenbusch demonstrated that bacteriorhodopsin forms small, well ordered three-dimensional crystals. The X-ray data indicate that the same two-dimensional crystals are present as formed by bacteriorhodopsin in its native environment (the purple membrane). These membranes are now stacked in the third dimension in a well ordered manner. Therefore, these crystals belong to type I.

The method has the conceptual problem that the growing three-dimensional crystal has to disrupt and displace the cubic lipidic phase. Nevertheless, it is hoped that this method can also be used for membrane proteins that do not have a strong tendency to form two-dimensional crystals spontaneously. In particular, this method appears to be the only chance for crystallizing those membrane proteins that are unstable in the absence of added lipids.


Landau, E. M. & Rosenbusch, J. P. (1996). Lipidic cubic phases: a novel concept for the crystallization of membrane proteins. Proc. Natl Acad. Sci. USA, 93, 14532–14535.
Lindblom, G. & Rilfors, L. (1989). Cubic phases and isotropic structures formed by membrane lipids – possible biological relevance. Biochim. Biophys. Acta, 988, 221–256.

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