Project description DEENESFRITPL Novel method for structural characterisation of membrane proteins Many human proteins are metalloproteins and require the binding of a metal or a metal-containing cofactor to function. Metalloproteins play a central role in metal ion transport, homeostasis, and redox reactions. Therefore, it is necessary to understand their molecular structure and biochemistry. Funded by the European Research Council, the P-MEM-NMR project aims to address the technical challenges associated with elucidating the structure and dynamics of integral membrane proteins. Researchers will optimise a recently pioneered magic-angle spinning nuclear magnetic resonance (MAS-NMR) method to unveil the structure-activity relationships in integral membrane metalloenzymes. The project will provide a widely applicable method for the structural characterisation of vital cellular processes, addressing contemporary challenges in molecular and chemical sciences. Show the project objective Hide the project objective Objective Integral membrane metalloproteins are involved in the transport and homeostasis of metal ions, as well as in key redox reactions that have a tremendous impact on many fields within life sciences, environment, energy, and industry. Most of our understanding of fine details of biochemical processes derives from atomic or molecular structures obtained by diffraction methods on single crystal samples. However, in the case of integral membrane systems, single crystals large enough for X-ray diffraction cannot be easily obtained, and the problem of structure elucidation is largely unsolved.We have recently pioneered a breakthrough approach using Magic-Angle Spinning Nuclear Magnetic Resonance (MAS-NMR) for the atomic-level characterization of paramagnetic materials and complex biological macromolecules. The proposed project aims to leverage these new advances through a series of new concepts i) to improve the resolution and sensitivity of MAS-NMR from nuclei surrounding a paramagnetic metal ion, such as e.g. cobalt, nickel and iron, and ii) to extend its applicability to large integral membrane proteins in lipid membrane environments. With these methods, we will enable the determination of structure-activity relationships in integral membrane metalloenzymes and transporters, by combining the calculation of global structure and dynamics with measurement of the electronic features of metal ions. These goals require a leap forward with respect to today’s protocols, and we propose to achieve this through a combination of innovative NMR experiments and isotopic labeling, faster MAS rates and high magnetic fields. As outlined here, the approaches go well beyond the frontier of current research. The project will yield a broadly applicable method for the structural characterization of essential cellular processes and thereby will provide a powerful tool to solve challenges at the forefront of molecular and chemical sciences today. Fields of science natural scienceschemical sciencesorganic chemistryorganic reactionsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsnatural sciencesphysical sciencesopticsspectroscopyabsorption spectroscopynatural scienceschemical sciencescatalysis Keywords Magic-Angle Spinning Nuclear Magnetic Resonance membrane proteins paramagnetic ions protein structure protein dynamics metal transporters metalloenzymes Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-CoG-2014 - ERC Consolidator Grant Call for proposal ERC-2014-CoG See other projects for this call Funding Scheme ERC-COG - Consolidator Grant Host institution CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS Net EU contribution € 2 499 375,00 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 € 2 499 375,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France Net EU contribution € 2 499 375,00 Address RUE MICHEL ANGE 3 75794 Paris 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 € 2 499 375,00
