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000062861 0247_ $$2DOI$$a10.1073/pnas.0712036105
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000062861 084__ $$2WoS$$aMultidisciplinary Sciences
000062861 1001_ $$0P:(DE-HGF)0$$aStöhr, J.$$b0
000062861 245__ $$aMechanisms of prion protein assembly into amyloid
000062861 260__ $$aWashington, DC$$bAcademy$$c2008
000062861 300__ $$a2409 - 2414
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000062861 440_0 $$05100$$aProceedings of the National Academy of Sciences of the United States of America$$v105$$x0027-8424$$y7
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000062861 520__ $$aThe 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.
000062861 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems$$cP33$$x0
000062861 588__ $$aDataset connected to Web of Science, Pubmed
000062861 650_2 $$2MeSH$$aAmyloid: chemistry
000062861 650_2 $$2MeSH$$aAmyloid: metabolism
000062861 650_2 $$2MeSH$$aAmyloid: ultrastructure
000062861 650_2 $$2MeSH$$aCircular Dichroism
000062861 650_2 $$2MeSH$$aCross-Linking Reagents: chemistry
000062861 650_2 $$2MeSH$$aDimerization
000062861 650_2 $$2MeSH$$aMicroscopy, Electron
000062861 650_2 $$2MeSH$$aPrions: chemistry
000062861 650_2 $$2MeSH$$aPrions: metabolism
000062861 650_2 $$2MeSH$$aPrions: ultrastructure
000062861 650_2 $$2MeSH$$aUltracentrifugation
000062861 650_7 $$00$$2NLM Chemicals$$aAmyloid
000062861 650_7 $$00$$2NLM Chemicals$$aCross-Linking Reagents
000062861 650_7 $$00$$2NLM Chemicals$$aPrions
000062861 650_7 $$2WoSType$$aJ
000062861 7001_ $$0P:(DE-HGF)0$$aWeinmann, N.$$b1
000062861 7001_ $$0P:(DE-HGF)0$$aWille, H.$$b2
000062861 7001_ $$0P:(DE-HGF)0$$aKaimann, K.$$b3
000062861 7001_ $$0P:(DE-Juel1)VDB72731$$aNagel-Steger, L.$$b4$$uFZJ
000062861 7001_ $$0P:(DE-Juel1)VDB65870$$aBirkmann, E.$$b5$$uFZJ
000062861 7001_ $$0P:(DE-HGF)0$$aPanza, G.$$b6
000062861 7001_ $$0P:(DE-HGF)0$$aPrusinder, S. B.$$b7
000062861 7001_ $$0P:(DE-HGF)0$$aEigen, M.$$b8
000062861 7001_ $$0P:(DE-HGF)0$$aRiesner, D.$$b9
000062861 773__ $$0PERI:(DE-600)1461794-8$$a10.1073/pnas.0712036105$$gVol. 105, p. 2409 - 2414$$p2409 - 2414$$q105<2409 - 2414$$tProceedings of the National Academy of Sciences of the United States of America$$v105$$x0027-8424$$y2008
000062861 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268150
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