Objectif Eukaryotic cells contain myriad signaling pathways used to transmit information from the plasma membrane to the nucleus. Given the large number of pathways in a cell, how is it that a given stimulus leads to a precise response? This problem is particularly acute in kinase pathways, such as mitogen-activated protein kinase (MAPK) cascades, which often share common protein components. Over the last decade, however, a paradigm that has emerged is that signaling pathway specificity can be mediated, in part, by scaffolding proteins that bind pathway members and restrict them to act only on one another. In yeast, as well as in mammals, several scaffold proteins for MAP-kinase cascades have been identified. These scaffolds allow one or more common kinases to function in distinct signaling pathways without improper cross-talk. However, very little is known about the mechanism by which these scaffold molecules physically control transmission of signaling information. We therefore plan to determine the three-dimensional structures of MAP-kinase modules of the yeast mating and high osmolarity response pathways, which are organized by two non-related scaffold proteins: Ste5 and Pbs2. The components (four kinases and two scaffold proteins) will be expressed as recombinant proteins and the complex reconstituted in vitro. We will use a multifaceted approach with the following specific aims: (1) to determine the structure of the reconstituted Ste5 and Pbs2 scaffolded complex by X-ray crystallography or electron cryomicroscopy and (2) to identify well-ordered fragments of the scaffolds that interact with individual member kinases to determine the structure of informative sub-complexes by X-ray crystallography. Champ scientifique natural sciencesearth and related environmental sciencesgeologymineralogycrystallographynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological scienceszoologymammalogy Mots‑clés Biological sciences Biology Natural sciences Structural biology 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) PEOPLE-2007-4-3.IRG - Marie Curie Action: "International Reintegration Grants" Appel à propositions FP7-PEOPLE-2007-4-3-IRG Voir d’autres projets de cet appel Régime de financement MC-IRG - International Re-integration Grants (IRG) Coordinateur EOTVOS LORAND TUDOMANYEGYETEM Contribution de l’UE € 100 000,00 Adresse EGYETEM TER 1-3 1053 Budapest Hongrie Voir sur la carte Région Közép-Magyarország Budapest Budapest Type d’activité Higher or Secondary Education Establishments Contact administratif Ferenc Hudecz (Prof.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
