Crystallization in Lipidic Cubic Phases

Abstract

Twenty to thirty percent of proteins coded by the genome are membrane proteins (1). They form pumps and channels in order to control and guide transport of ions and metabolites. Other membrane proteins function as receptors and are responsible for molecular recognition of hormones and neurotransmitters. In spite of strong efforts, it is extremely difficult to crystallize these proteins and only a few different integral membrane proteins have been crystallized so far (2) and modeled at high resolution (see http://www.mpibpfrankfurt.mpg.de/michel/public/memprotstruct.html). Even in the case of water soluble proteins, for which good approaches to crystallization have been established, considerable efforts are necessary to search for the proper crystallization conditions by screening over a wide range of different parameters (pH, ionic strength, precipitants, protein concentration, etc.). In the case of membrane proteins, one faces even greater problems. Membrane proteins are amphiphilic in nature; in order to be solubilized the use of detergents is inevitable. A major obstacle to overcome is finding the detergent that preserves the stability of the protein. Unfortunately, “what seems to be suited for crystallization of membrane proteins is less suited for their stability” (3).