Objective Amyloid fibrils are self-assembled filamentous structures associated with a wide variety of severely debilitating human pathologies like Alzheimers disease, type II diabetes and the transmissible spongiform encephalopathies. Despite the immense medical importance of amyloid fibrils, no atomic-resolution structures are available for these materials yet. The aim of the project is to determine the structure of the carboxy-terminal part of the prion protein HET-s in its fibrillar state using solid-state NMR.For this fragment, the structure-infectivity correlation has been established, and the host laboratory has already collected information about secondary structure elements. Solid-state NMR is to date the only technique capable of obtaining the structure of such non-crystalline compounds. The state-of-the art methods in solid-state NMR of the host will be combined with the knowledge of the fellow in liquid crystal NMR to provide accurate structural restraints and obtain a structure at atomic resolution. In particular, new NMR experiments will be implemented using fully labelled and axially oriented protein samples. The information obtained by solid-state NMR will be completed with Electron Diffraction and Atomic Force Microscopy data. The results for the HET-s fibrillar system will give a detailed molecular explanation of the characteristic properties of the amyloid fibrils, in particular their unusual stability. This will help designing new drugs against amyloid diseases. Fields of science medical and health sciencesbasic medicineneurologydementiaalzheimernatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesmicrobiologymycologynatural sciencesphysical sciencesopticsmicroscopyengineering and technologymaterials engineeringliquid crystals Keywords Amyloid fibrils HET HET-s prion protein Solid-state NMR Structure determination Structure determination. Amyloid fibrils debilitating human pathologies high high-resolution spectra liquid crystals long long-ranged constraints new NMR methodology ranged constraints resolution spectra s prion protein. Solid state NMR Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2005-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator EIDGENOSSICHE TECHNISCHE HOCHSCHULE, ZURICH Address Raemistrasse 101 Zurich Switzerland See on map Links Website Opens in new window EU contribution No data
