% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Sthr:62861, author = {Stöhr, J. and Weinmann, N. and Wille, H. and Kaimann, K. and Nagel-Steger, L. and Birkmann, E. and Panza, G. and Prusinder, S. B. and Eigen, M. and Riesner, D.}, title = {{M}echanisms of prion protein assembly into amyloid}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {105}, issn = {0027-8424}, address = {Washington, DC}, publisher = {Academy}, reportid = {PreJuSER-62861}, pages = {2409 - 2414}, year = {2008}, note = {Record converted from VDB: 12.11.2012}, abstract = {The conversion of the alpha-helical, cellular isoform of the prion protein (PrP(C)) to the insoluble, beta-sheet-rich, infectious, disease-causing isoform (PrP(Sc)) is the key event in prion diseases. In an earlier study, several forms of PrP were converted into a fibrillar state by using an in vitro conversion system consisting of low concentrations of SDS and 250 mM NaCl. Here, we characterize the structure of the fibril precursor state, that is, the soluble state under fibrillization conditions. CD spectroscopy, analytical ultracentrifugation, and chemical cross-linking indicate that the precursor state exists in a monomer-dimer equilibrium of partially denatured, alpha-helical PrP, with a well defined contact site of the subunits in the dimer. Using fluorescence with thioflavin T, we monitored and quantitatively described the kinetics of seeded fibril formation, including dependence of the reaction on substrate and seed concentrations. Exponential, seed-enhanced growth can be achieved in homogeneous solution, which can be enhanced by sonication. From these data, we propose a mechanistic model of fibrillization, including the presence of several intermediate structures. These studies also provide a simplified amplification system for prions.}, keywords = {Amyloid: chemistry / Amyloid: metabolism / Amyloid: ultrastructure / Circular Dichroism / Cross-Linking Reagents: chemistry / Dimerization / Microscopy, Electron / Prions: chemistry / Prions: metabolism / Prions: ultrastructure / Ultracentrifugation / Amyloid (NLM Chemicals) / Cross-Linking Reagents (NLM Chemicals) / Prions (NLM Chemicals) / J (WoSType)}, cin = {INB-2}, ddc = {000}, cid = {I:(DE-Juel1)VDB805}, pnm = {Funktion und Dysfunktion des Nervensystems}, pid = {G:(DE-Juel1)FUEK409}, shelfmark = {Multidisciplinary Sciences}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:18268326}, pmc = {pmc:PMC2268150}, UT = {WOS:000253469900031}, doi = {10.1073/pnas.0712036105}, url = {https://juser.fz-juelich.de/record/62861}, }