The work has been supported by the EU-funded projects UPMAN and EU-NMR and by the DFG-funded Cluster of Excellence: Macromolecular Complexes. The Center for Biomolecular Magnetic Resonance is funded by the state of Hesse. The authors acknowledge valuable discussion with S. Hornemann and V. Dötsch.
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Communication
Unfolded-State Structure and Dynamics Influence the Fibril Formation of Human Prion Protein†
Article first published online: 30 OCT 2009
DOI: 10.1002/anie.200903771
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Gerum, C., Silvers, R., Wirmer-Bartoschek, J. and Schwalbe, H. (2009), Unfolded-State Structure and Dynamics Influence the Fibril Formation of Human Prion Protein. Angewandte Chemie International Edition, 48: 9452–9456. doi: 10.1002/anie.200903771
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Publication History
- Issue published online: 30 NOV 2009
- Article first published online: 30 OCT 2009
- Manuscript Revised: 21 AUG 2009
- Manuscript Received: 9 JUL 2009
Funded by
- EU
- DFG
Keywords:
- conformational dynamics;
- human prion protein;
- NMR spectroscopy;
- protein structures
Graphical Abstract
Rigid bridges: NMR studies of the unfolded state (U) of the human prion protein (PrP) show that in the oxidized form the native disulfide bridge between two cysteine residues rigidifies the surrounding amino acids. This area is a hotspot region of the protein in terms of disease-related mutations that promote aggregation and formation of the abnormal “scrapie” form (PrPSc).