CRYSTALLIZATION OF MEMBRANE-PROTEINS - A MINIREVIEW

Over ten years ago, the first reports appeared, demonstrating that membrane proteins could be crystallized [H. Michel and D. Oesterhelt, Proc; Natl. Acad. Sci. USA 77 (1980) 1283; R.M. Caravito and J.P. Rosenbusch, J. Cell Biol. 86 (1980) 327]. In the past decade, other research groups have successfully prepared large single crystals of integral membrane proteins for X-ray diffraction analysis. While no simple set of methods yet exists, the general strategies for designing membrane protein crystallization experiments have become clearer. All X-ray quality crystals of membrane proteins were grown from preparations of detergent-solubilized protein, using standard crystallization methods for soluble proteins. In this article, we discuss the roles of the detergent, salt, and precipitant in the crystallization process and the adaption of published protocols to new membrane protein systems. We focus on the polyethylene glycol/NaCl/beta-octyl glucoside system as a general model and show that the presence of detergent applies several types of constraints to the crystallization conditions. The general conclusion is that many integral membrane proteins could be crystallized if pure and monodisperse protein solutions in a suitable detergent system can be prepared.