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Schwarzinger, Stephan ; Horn, Anselm H. C. ; Ziegler, Jan ; Sticht, Heinrich:
Rare large scale subdomain motions in prion protein can initiate aggregation.
In: Journal of Biomolecular Structure & Dynamics.
Bd. 23
(2006)
Heft 6
.
- S. 581-590.
ISSN 1538-0254
DOI: https://doi.org/10.1080/07391102.2006.10507083
Abstract
The prion protein is thought to induce prion diseases by changing its conformation from the cellular form, PrP(C), into the infectious Scrapie-form, PrP(Sc). Little is known about the structural and dynamical features of this conformational change. We here introduce a novel concept that involves rare large scale motions between the subdomains beta1-alpha1-beta2 and alpha2-alpha3 in the carboxy-terminal, globular part of PrP. The interface between these two subdomains carries most pathogenic mutations known to be associated with prion diseases. Based on computational simulations as well as experimental results we propose that such a large scale motion subsequently destabilizes large parts of the cellular conformer PrP(C), thus, rendering it prone to structural rearrangements, including aggregation of now partially unfolded parts of the PrP sequence. We hypothesize that such large scale motions occur as a rare event even under equilibrium conditions and that the interaction of such partially destabilized PrP(C)-conformers, which we named PrP(C*), contributes to the formation of pathogenic oligomeric species of the prion protein.
Weitere Angaben
| Publikationsform: | Artikel in einer Zeitschrift |
|---|---|
| Begutachteter Beitrag: | Ja |
| Institutionen der Universität: | Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Ehemalige Professoren > Lehrstuhl Biopolymere - Univ.-Prof. Dr. Paul Rösch Fakultäten Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Ehemalige Professoren Fakultäten > Fakultät für Biologie, Chemie und Geowissenschaften > Fachgruppe Chemie > Lehrstuhl Biochemie mit Schwerpunkt Biophysikalische Chemie |
| Titel an der UBT entstanden: | Ja |
| Themengebiete aus DDC: | 500 Naturwissenschaften und Mathematik > 540 Chemie 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften; Biologie |
| Eingestellt am: | 29 Jan 2019 07:46 |
| Letzte Änderung: | 16 Mai 2019 05:37 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/47099 |