التفاصيل البيبلوغرافية
| العنوان: |
Structural insights into fibrillar proteins from solid-state NMR spectroscopy ; Études structurales des protéines fibrillaires par spectroscopie de RMN à l’état solide |
| المؤلفون: |
Habenstein, Birgit |
| المساهمون: |
Lyon 1, Böckmann, Anja |
| المصدر: |
Theses.fr |
| سنة النشر: |
2011 |
| مصطلحات موضوعية: |
RMN à l’état solide, Attribution des résonances RMN, Prion, Protéines fibrillaires, Structure tridimensionnelle des protéines, Solid-state NMR, NMR resonance assignment, Fibrillar proteins, 3D protein structure, stat, envir |
| الوصف: |
Solid-state NMR is the method of choice for studies on insoluble proteins and other high molecular weight protein complexes. The inherent insolubility of fibrillar proteins, as well as their complex architecture, makes the application of x-ray crystallography and solution state NMR difficult. Solid-state NMR is not limited by the molecular weight or by the absence of long-range structural order, and is thus a powerful tool for the 3D structural investigation of fibrillar proteins. The assignment of the NMR resonances is a prerequisite to obtain structural information at atomic level. The first part of this thesis describes the development of solid-state NMR methods to assign the resonances in large proteins. We apply these methods to assign the 33 kDa C-terminal domain of the Ure2p prion which is up to now the largest protein assigned by solid-state NMR. Our results provide the basis to study high molecular weight proteins at atomic level. This is demonstrated in the second part with the first high-resolution solid-state NMR study of Ure2 and Sup35 prion fibrils. We describe the conformation of the functional domains and prion domains in the full-length fibrils and in isolation. The third fibrillar protein addressed in this work is the Parkinson’s disease related α-synuclein whereof we demonstrate the NMR resonance assignment and the secondary structure determination of a new polymorph. Thus, the studies described here provide new insights in the structural diversity of fibril architectures, and plead to view fibrils as individuals from a structural point of view, rather than a homogenous protein family ; La RMN à l’état solide est une méthode de choix pour l’étude des protéines insolubles et des complexes protéiques de haut poids moléculaire. L’insolubilité intrinsèque des protéines fibrillaires, ainsi que leur architecture complexe, rendent difficile leur caractérisation structurale par la cristallographie et par la RMN en solution. La RMN à l‘état solide n’est pas limitée par le poids moléculaire et constitue ... |
| نوع الوثيقة: |
thesis |
| اللغة: |
English |
| العلاقة: |
10670/1.yusn9p; http://www.theses.fr/2011LYO10212Test |
| الإتاحة: |
http://www.theses.fr/2011LYO10212Test |
| حقوق: |
other |
| رقم الانضمام: |
edsbas.67C48644 |
| قاعدة البيانات: |
BASE |
