Lipidic cubic phase crystallization is a well-established alternative to vapour diffusion crystallization, especially for membrane proteins. However, space limitations of the water channels have made the technique inaccessible for membrane proteins with larger extra- or intracellular domains.
DSPG is an anionic phospholipid applied in combination with Monopalmitolein to create an ultra-swollen lipidic mesophase for the crystallization of membrane proteins with large extracellular domains.
This specific lipid mixture results in lipidic mesophases with the following advantages:
Zabara et al. have used this approach to crystallize GLIC, a pentameric membrane protein with a large extracellular domain, for the first time using the in meso method (PDB ID 6F7A). Crystals grew in a new space group with tighter packing and less solvent content.
Figure from , used courtesy of Prof. Raffaele Mezzenga, ETH Zurich
Normal vs. swollen mesophases and the GLIC protein structure. Schematic illustrations of
a normal Pn3m cubic mesophase composed of Monopalmitolein : water,
b GLIC protein structure, and
c in meso crystallization of GLIC protein in a highly swollen Pn3m cubic mesophase composed of DSPG : Monopalmitolein : water.
Note the difference in size of the lipid bilayer scale bar, which is 30 Å, on a and c panels
 Zabara et al. (2018) Design of ultra-swollen lipidic mesophases for the crystallization of membrane proteins with large extracellular domains. Nat. Commun. 9:544.