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| GEBHARD F.X. SCHERTLER | |
| G protein-coupled receptor activation and signalling |
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Structure of rhodopsin in a trigonal crystal form. |
G protein-coupled receptors comprise the largest gene family in the human genome. They are central to neurobiology, pharmacology and sensory physiology. The visual system is by far the best-studied system at the molecular level and at the level of brain organisation.
Working at the molecular level, in collaboration with Jade Li we have determined the structure of rhodopsin by X-ray crystallography and electron microscopy. Our structures have important new implications for the G protein-binding surface of unactivated rhodopsin. The most important question left in the field is the molecular mechanism of G protein-coupled receptor activation. For this we will need the structure of the activated receptor in complex with other signalling molecules. We will therefore develop biochemical protocols to isolate rhodopsin/transducin, rhodopsin/rhodopsin kinase, and rhodopsin/arrestin complexes using native and recombinant proteins and will crystallise these signalling complexes. In contrast to other systems, the components of the visual system are well characterised and available from native sources as well as expression systems. We will crystallise the signalling complexes and solve their structure with the most advanced X-ray and electron microscopy techniques available. From these structures we will gain insight into the general activation mechanism of G protein-coupled receptors. This mechanism is of crucial importance for the regulation of neurobiological processes and it might give new possibilities for pharmacological intervention. |
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Unger, V.M., Hargrave, P.A., Baldwin, J.M. & Schertler, G.F.X. (1997) Li, J., Edwards, P., Burghammer, M., Villa, C. & Schertler, G.F.X. (2004) Ruprecht, J., Mielke, T., Vogel, R.,Villa, C. & Schertler, G.F.X. (2004) |
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