SSNMR-AMYLOIDS · Amyloid fibril structures explored by solid-state NMR
6РП — Действия „Мария Кюри“
- Период
- 2006-12-01 → 2008-11-30
- Финансиране от ЕС
- 173 264 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Амилоидните влакна, като тези при гъбата Podospora anserina, се изследват чрез ядромно магнитен резонанс в твърдо състояние. Това помага да се разбере структурата и стабилността на протеините, свързани с различни заболявания при хората и животните.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - SSNMR-Amyloids (Amyloid fibril structures explored by solid-state NMR.)
Prions and amyloid fibrils are associated with several animal and human diseases. Despite the paramount importance of the structural aspects, no atomic resolution structure of a prion in its fibrillar state had been reported. Solid-state NMR is to date the only technique capable of obtaining the structure of such non-crystalline and non-soluble compounds. We have obtained the structure of amyloid fibrils produced in vitro from the prion-forming domain (residues 218-289) of the HET-s prion from the filamentous fungus Podospora anserina using solid-state NMR techniques. These results give a structural explanation of the stability of the amyloid fibrils. The HET-s(218-289) prion forms a left-handed beta-solenoid, of which each molecule represents two helical windings. This beta-solenoid is stabilized not only by the H-bond network formed by the parallel stacking of the beta-strands, but also by three salt-bridges, two asparagine-ladders, and the presence of a solvent-protected rigid triangular hydrophobic core. Furthermore, an improved protocol for structure determination of amyloid fibrils using solid-state NMR techniques is proposed on this example.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
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.
Оригинален текст от CORDIS (на английски).
Участници
- EIDGENOSSICHE TECHNISCHE HOCHSCHULE, ZURICH · ZURICHКоординаторНиво градШвейцария
Връзки
Данни: CORDIS, © Европейски съюз