Semliki Forest virus vectors: versatile tools for efficient large-scale expression of membrane receptors

Abstract

One of the prerequisites for success in structural biology is to have access to large quantities of the protein of interest to enable purification and crystallization and furthermore to carry out high-resolution structural analysis. It is well known that only rarely, as in the case of rhodopsin, the protein concentration in native tissue is high enough to allow direct purification of material for structural studies. Particularly, transmembrane receptors are expressed at a rather low density and so far, among seven transmembrane receptors, only bacteriorhodopsin [1] and bovine rhodopsin [2, 3] have been successfully purified, crystallized and high-resolution structures resolved. There is, however, an enormous interest in the structural biology of receptors belonging to the family of G-protein coupled receptors (GPCRs) because many of these are involved in neurotransmission and important signal transduction events specifically in nerve cells. For this reason, GPCRs are the target molecules for intensive research to develop novel drugs for many central nervous system disorders including anxiety, depression and memory dysfunction.