Objective Extrapolating from protein structure to function is an operation difficult to accomplish, as most functions in the cell are not carried out by single proteins, but by macromolecular complexes containing multiple subunits endowed with specific functions. Despite the many advances in structural and biochemical studies of isolated molecules, a comprehensive portrait of cell biochemistry must thus include insights of the supramolecular network of interactions among the individual constituents. The structure determination of large and dynamical protein ensembles presents a great deal of challenges for X-ray diffraction techniques, and for solution nuclear magnetic resonance (NMR) due to the large size of these objects. Consequently, there is little information available today on the overall organization of the assembly subunits, their interactions, and sometimes their precise function within the cell. High-resolution solid-state NMR (ssNMR) has recently developed as a powerful structural tool for studying structure and dynamics of solid biological samples at atomic resolution. A number of issues remain however to be addressed before ssNMR is ready to cope with large-sized multi-domain functional assemblies.The proposed project aims to capitalize on new concepts recently introduced by the host institution, to implement innovative solid-state NMR methodologies. Sophisticated experimental approaches will be introduced at high magnetic field, in combination with ultra-fast magic angle spinning (MAS), enabling the structure characterization of non-crystalline assemblies that cannot be currently carried out by any other experimental technique, and notably, the determination at atomic level of the structural details that govern protein-protein interactions in functional assemblies. As a benchmark, we will tackle the interaction mode of the ring-shaped hexameric DnaB helicase with its partner DnaC, an assembly that controls the origin of the DNA replication in E. coli. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsnatural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acidsnatural sciencesbiological sciencesmicrobiologybacteriologynatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesgeneticsRNA Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Net EU contribution € 185 076,00 Address RUE MICHEL ANGE 3 75794 Paris France See on map Region Ile-de-France Ile-de-France Paris Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 185 076,00
