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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year

IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

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Volume 382, Issue 4


Structural Intermediates in the Putative Pathway from the Cellular Prion Protein to the Pathogenic Form

Katja Jansen / Oliver Schäfer / Eva Birkmann / Karin Post / Hana Serban / Stanley B. Prusiner / Detlev Riesner
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/BC.2001.081


The conversion of the αhelical, protease sensitive and noninfectious form of the prion protein (PrP) into an insoluble, protease resistant, predominantly βsheeted and infectious form (PrP) is the fundamental event in prion formation. In the present work, two soluble and stable intermediate structural states are newly identified for recombinant Syrian hamster PrP(90 231) (recPrP), a dimeric αhelical state and a tetra or oligomeric, βsheet rich state. In 0.2% SDS at room temperature, recPrP is soluble and exhibits αhelical and random coil secondary structure as determined by circular dichroism. Reduction of the SDS concentration to 0.06% leads first to a small increase in αhelical content, whereas further dilution to 0.02% results in the aquisition of βsheet structure. The reversible transition curve is sigmoidal within a narrow range of SDS concentrations (0.04 to 0.02%). Size exclusion chromatography and chemical crosslinking revealed that the αhelical form is dimeric, while the βsheet rich form is tetra or oligomeric. Both the αhelical and βsheet rich intermediates are soluble and stable. Thus, they should be accessible to further structural and mechanistic studies. At 0.01% SDS, the oligomeric intermediates aggregated into large, insoluble structures as observed by fluorescence correlation spectroscopy. Our results are discussed with respect to the mechanism of PrP formation and the propagation of prions.

About the article

Published Online: 2005-06-01

Published in Print: 2001-04-27

Citation Information: Biological Chemistry, Volume 382, Issue 4, Pages 683–691, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/BC.2001.081.

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