SSNMR-AMYLOIDS - Amyloid fibril structures explored by solid-state NMR.
2006-12-01 - 2008-11-30
Marie Curie Actions (MCA)
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-labeled 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.
Beat H. Meier
Eidgenossische Technische Hochschule Zuerich
Other FP6 priorities
Diabetes Mellitus, Non-Insulin-Dependent
Gamete Intrafallopian Transfer
Magnetic Resonance Imaging
Nuclear Magnetic Resonance
Protein Structure, Secondary
Microscopy, Atomic Force
SAFB protein, human
Last updated on 2011-08-18 at 19:12