It’s a catch-22: Crystallizing membrane proteins requires the use of detergent molecules, but protein crystals grown with detergents are often of poor quality. To solve the dilemma, a multi-institutional team led by Qinghai Zhang of Scripps Research Institute California has improved upon a previously reported class of detergent molecules known as facial amphiphiles. The new amphiphiles stabilize membrane proteins from different families and form high-quality three-dimensional crystals (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.1221442110). The molecules consist of sugar-containing chains attached to one face of the steroid cholate. The identity, number, and position of polar groups on the amphiphiles strongly affect the molecules’ ability to stabilize membrane proteins, the researchers note. The new amphiphiles associate tightly with membrane proteins to form small complexes that enhance the crystallizability of the proteins. The researchers crystallized various membrane proteins with the amphiphiles, including bacteriorhodopsin from Halobacterium salinarum, the transporter protein MsbA from Escherichia coli, the human channel protein connexin 26, and several cytochrome P450 enzymes.