A pedestrian guide to membrane protein crystallization

Membrane protein structural biology is a frontier area of modern biomedical research. Twenty to thirty-five percent of the proteins encoded by an organism's genome are integral membrane proteins. Integral membrane proteins, such as channels, transporters, and receptors, are critical components of many fundamental biological processes. Also, many integral membrane proteins are important in biomedical and biotechnological applications; the majority of drug targets are integral membrane proteins. The sharp increase in the number of membrane protein structures over the last several years gives some indication that this field is poised for rather explosive growth as more and more investigators take on membrane protein projects. The purpose of this brief practical review was to take a snapshot of a field at the onset of its likely exponential growth phase, and to lay out the methods that have worked to date for obtaining membrane protein crystals suitable for structure determination by X-ray crystallography. Many of the successful experimental methods are identical to those used for soluble proteins. The major difference, and a non-trivial difference, is the necessity for inclusion of detergents above the critical micelle concentration in the purified membrane protein solution.