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Content archived on 2024-05-29

Amyloid fibril structures explored by solid-state NMR

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 (EuroSciVoc)

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Topic(s)

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Call for proposal

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FP6-2005-MOBILITY-5
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Funding Scheme

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EIF - Marie Curie actions-Intra-European Fellowships

Coordinator

EIDGENOSSICHE TECHNISCHE HOCHSCHULE, ZURICH
EU contribution
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Total cost

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