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3D organization of yeast MAP-kinase modules

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 (EuroSciVoc)

Mots‑clés

Programme(s)

Thème(s)

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
Région
Közép-Magyarország Budapest Budapest
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
Aucune donnée