The structural characterisation of G-protein coupled receptors (GPCRs) is of major importance for biology, pharmacology and medicine. Problems associated with the expression, solubilisation and purification of many of the most interesting eukaryotic GPCRs has until now hindered progress.
The MePNet consortium is in a unique position to move this area forward. First part of our research has been very successful in achieving overexpression and characterisation of a number of GPCRs. Furthermore, it has been possible to solubilise and purify several of these receptors.
The focus of 2005-2007 research now shift to crystallisation of GPCRs. Large scale production of 7 purified receptors have began to feed the intensive crystallisation screening program. 20 to 30 additional receptors will be processed when expression and/or purification conditions are optimised. This will be based on experimental screens for receptor isolation from membranes. Crystallisation trials aim to exploit the interactions between individual receptors and their cognate ligands, G-proteins and arrestins in order to improve the possibility of obtaining stable protein, the key to successful crystallisation.
These features together with the expertise within the consortium provide MePNet with the best possible foundation for solving GPCR structures within 2008.