Figure 1.

Cartoon representation of the events proposed to take place during the crystallization of an integral membrane protein from the lipidic cubic mesophase. The process begins with the protein reconstituted into the curved bilayer of the `bicontinuous' cubic phase (tan). Added `precipitants' shift the equilibrium away from stability in the cubic membrane. This leads to phase separation wherein protein molecules diffuse from the bicontinuous bilayered reservoir of the cubic phase into a sheet-like or lamellar domain (A) and locally concentrate therein in a process that progresses to nucleation and crystal growth (B, from reference 9). Cocrystallization of the protein with native lipid (cholesterol) is shown in this illustration. As much as possible, the dimensions of the lipid (tan oval with tail), detergent (pink oval with tail), cholesterol (purple), protein (blue and green; β₂-adrenergic receptor-T4 lysozyme fusion; PDB code 2RH1), bilayer and aqueous channels (dark blue) have been drawn to scale. The lipid bilayer is ~40 Å thick.