Membrane Protein Won’t Crystallize? Try This

Many of the X-ray crystal structures of pharmaceutically important G protein-coupled receptors wouldn’t exist if it weren’t for lipidic cubic phases, transparent gel-like matrices designed to provide an environment like that of a cell membrane. Although these matrices work well at 20 °C, they rarely remain stable at lower temperatures, a limitation when working with finicky membrane proteins such as the neurotensin receptor. Most lipidic cubic phases are made from commercially available lipids. Recognizing an opportunity for chemists to build designer lipids, Jay. S. Siegel of Tianjin University, Raffaele Mezzenga of ETH Zurich, and Ehud M. Landau of the University of Zurich teamed up. Grad student Livia Salvati Manni and postdoc Alexandru Zabara replaced the olefin on monoolein, the best-studied lipid that forms lipidic cubic phases, with a cyclopropyl group. They obtained monodihydrosterculin (MDS), a more rigid molecule that forms a stable lipidic cubic phase at 4 °C (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201409791). With Andreas Plückthun of the University of Zurich, the team has used the lipid to crystallize the membrane protein bacteriorhodopsin.