Vast amounts of money are being spent on drugs acting on membrane proteins without knowledge of the molecular details of their mode of action. Even though the genes of membrane proteins are now accessible, solving their structure remains time-consuming and often unsuccessful. Given their physiological and biomedical importance, this constitutes a major problem in basic life sciences as well as public health care. Tools have been developed to overexpress, solubilize, stabilize, purify and crystallize membrane proteins, and they are currently being used in large-scale initiatives for structure determination. Unfortunately, most membrane proteins resist one or more of these steps. The objective of IMPS is to develop imaginative, broad-range tools for membrane structural proteomics. The project brings together experts in chemistry, biochemistry, molecular genetics and crystallography and aims at developing original, innovative tools to attack each of these stumbling blocks. A strong core of crystallographers with demonstrated expertise in membrane protein structure determination will apply these novel techniques to a representative test set of membrane proteins. The approaches to be developed include original overexpression systems (insect photoreceptor cells and the chloroplast), unconventional surfactants (amphipathic polymers, fluorinated surfactantns, novel detergents and additives) and unconventional crystallizaton systems (lipid cubic phase crystallization, other non-detergent environments, molecular scaffolding, bicelles). These novel methodologies will be made available to the community through a distributed technological platform including workshops, hands-on training, and diessemination of the new molecules, whose large-scale synthesis and distribution will be carried out by a participant SME. The circulation of scientist between IMPS lobaratories will guarantee the rapid spread of the new know-how.
