Structural genomics of “non-standard” proteins: a chance for membrane proteins?

Abstract

Between one quarter and one third of all genes in eu- and prokaryotic organisms code for integral membrane proteins. Despite their eminent biological roles structural genomics projects so far excluded this class of proteins, mostly because of their amphiphilic character that imposes a variety of “non-standard” requirements for protein expression, purification, detergent-dependent solubilisation, and crystallization. Consequently, major obstacles for the structure determination of integral membrane proteins are the low success rates of 3D-crystallization and the number of membrane proteins which are available in amounts suitable for structural studies. While a variety of crystallization techniques for membrane proteins were developed during the last decade, no systematic approaches have yet been applied to augment the supply of new membrane proteins as candidates for 3D-crystallization. Several pilot projects applying structural genomics strategies on membrane proteins have now been initiated to close the increasing gap between genomic and structural information for this protein class.