Objetivo "Over the last decade it has become increasingly clear that a large fraction (up to 40%) of the proteins encoded by the human genome are disordered. Intrinsically disordered proteins (IDPs) remain functional despite a lack of a well-defined structure, such that the classical structure-function paradigm breaks down, and new insight into the relationship between primary sequence and molecular function is necessary. The object of this proposal is to study the role of IDPs in the replication and transcription of Measles (MeV) and Sendai viruses (SeV). Replication and transcription of the viral RNA in these related paramyxoviridiae is initiated by an interaction between the intrinsically disordered C-terminal domain, NTAIL, of the nucleoprotein and the highly flexible C-terminal domain, PX, of the phosphoprotein. Upon binding to PX, both NTAIL proteins undergo alpha-helical folding of the molecular recognition element, positioned at the C-terminal end of the unfolded domain of the nucleoprotein. To fully understand the molecular basis of this interaction, and to determine the role of the disordered domains, atomic resolution models of the proteins are necessary in their free, pre-recognition states and in complex with their partner proteins. In order to achieve this aim I will use high field solution state NMR, small angle neutron and X-ray scattering and molecular modeling. Due to its inherent flexibility solution state NMR studies of the NTAIL domain will also be performed in the context of the entire 13C/15N labeled nucleocapsid (particles whose size ranges from 10-500MD). These particles will be further studied using solid state NMR and electron microscopy. This system represents a paradigm of intermolecular interaction involving highly flexible proteins and will therefore reveal features of transient folding upon binding in IDPs, while shedding new light on viral replication molecular mechanisms whose comprehension is crucial for the design of new antiviral drugs." Ámbito científico natural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesphysical sciencesopticsmicroscopyelectron microscopynatural sciencesbiological sciencesgeneticsRNAnatural sciencesphysical sciencesopticsspectroscopy Programa(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) Tema(s) FP7-PEOPLE-2010-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Convocatoria de propuestas FP7-PEOPLE-2010-IEF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IEF - Intra-European Fellowships (IEF) Coordinador CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Aportación de la UE € 185 248,00 Dirección RUE MICHEL ANGE 3 75794 Paris Francia Ver en el mapa Región Ile-de-France Ile-de-France Paris Tipo de actividad Research Organisations Contacto administrativo Jean-Xavier Boucherle (Dr.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos
