Objectif Small GTPases of the Ras superfamily, a major class of signalling proteins, control critical cellular functions, such as proliferation, differentiation, migration and trafficking. Their misregulation is associated with severe diseases, such as cancer or neurodegenerative diseases. More than 150 Ras-like GTPase are known, which are divided into four major subfamilies, each containing between 22 to 63 structurally related, but functionally distinct isoforms. A fundamental unresolved biological question in the field is the structure-based mechanism, which guides isoform specific functions. Recently, we provided new structural insight on how Ras operates in the context of the membrane. We showed that Ras adopts isoform specific orientations on the membrane, which in turn critically regulate Ras activity. These orientations are guided by a new switch III region and are stabilized by the amphipathic helix α4 and the membrane anchoring, C-terminal HyperVariable Region (HVR). Intriguingly, these structural elements vary from one isoform to another also in other subfamilies, suggesting that this mechanism is also operative in them. We will therefore study, whether this mechanism that involves helix α4 and the HVR also define isoforms of the Rho- and Rab-subfamily. In parallel, we will investigate the molecular mechanisms that are relevant for the overall membrane organisation of GTPases. This includes studies on the dynamics of the orientation, as well as on the mechanism of the formation of nanoscale assemblies (nanoclusters) of GTPases on the membrane. We expect that our results have the potential to substantially transform the current understanding of GTPase functioning and answer a long-standing fundamental biological question. Moreover, both mechanisms represent new, specific targets for pharmacological interventions. Champ scientifique natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Appel à propositions FP7-PEOPLE-2010-RG Voir d’autres projets de cet appel Régime de financement MC-IRG - International Re-integration Grants (IRG) Coordinateur ABO AKADEMI Contribution de l’UE € 100 000,00 Adresse DOMKYRKOTORGET 3 20500 Abo Finlande Voir sur la carte Région Manner-Suomi Etelä-Suomi Varsinais-Suomi Type d’activité Higher or Secondary Education Establishments Contact administratif Tiina Haanila (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée