Applications and dissemination
Working group chair – Manuela Pereira (Portugal)
This WG will provide a forum for dissemination and application of the techniques developed in WGs1-4. In this WG, a firm two-way link with biological research groups will be established that enables both the provision of model systems for methods development in WGs1-4 as well as high impact, and especially medically relevant, biological systems for which a high resolution structural and dynamic description is needed. These relevant systems include membrane transporters including multidrug resistance (MDR) transporters, membrane receptors (G protein coupled receptors, GPCRs), which are the target of many administered drugs as well as molecular machines and large macromolecular complexes. This WG will also provide a link to chemical and medicinal chemical researchers able to make use of such dynamic structural information for the development of new drugs and biotechnological tools. The following systems have been identified as excellent candidates for one or more of the methodological approaches detailed in this Action: membrane transporters, GPCRs, virus assembly/disassembly, proton-coupled electron transfer, and large macromolecular machines. The key questions to be addressed are: a) the mechanism of membrane transport including the conformational rearrangement of the transport cycle as well as substrate and inhibitor binding to the transporters, b) the mechanism and the dynamics of signal transduction of GPCRs and the regulation of G-proteins, c) the role of RNA and interacting proteins for virus assembly/disassembly, the site of drug action and the proteins and conformations involved, d) the movement of domains, their regulation and coupling mechanisms in proton-coupled electron transfer, as well as e) subunit movement and sequence of events in catalysis and force generation of large molecular machines (e.g. molecular motors, FAS, PKS, actin cytoskeleton and ribosome).
Working group objectives
1) To exchange information with the technologists and ask specific key biological questions for which new experimental approaches are required and need to be developed.
2) To educate researchers from WGs1-4 in Training Schools and Workshops hence improving their fundamental understanding of the systems under study.
3) Dissemination of results in conferences and in high impact journals.
WG5 will have the specific goals:
1) To provide high quality samples for method development groups of WG1-3.
2) To apply the novel techniques (developed in WG1-4) to gain insights which were not achievable before.
3) To develop a specific understanding at the molecular level of structures, dynamics and conformational changes inherent in the function of these molecular machines.