This title appears in the Scientific Report :
2011
Please use the identifier:
http://dx.doi.org/10.1515/BC.2011.048 in citations.
Please use the identifier: http://hdl.handle.net/2128/18354 in citations.
In vitro conversion and seeded fibrillization of posttranslationally modified prion protein
In vitro conversion and seeded fibrillization of posttranslationally modified prion protein
The conversion of the cellular isoform of the prion protein (PrP(C)) into the pathologic isoform (PrP(Sc)) is the key event in prion diseases. To study the conversion process, an in vitro system based on varying the concentration of low amounts of sodium dodecyl sulfate (SDS) has been employed. In t...
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Personal Name(s): | Stöhr, J. |
---|---|
Elfrink, K. / Weinmann, N. / Wille, H. / Willbold, D. / Birkmann, E. / Riesner, D. | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | Biological chemistry, 392 (2011) S. 415 - 421 |
Imprint: |
Berlin [u.a.]
de Gruyter
2011
|
Physical Description: |
415 - 421 |
PubMed ID: |
21476870 |
DOI: |
10.1515/BC.2011.048 |
Document Type: |
Journal Article |
Research Program: |
BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung Funktion und Dysfunktion des Nervensystems |
Series Title: |
Biological Chemistry
392 |
Subject (ZB): | |
Link: |
Get full text OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/18354 in citations.
The conversion of the cellular isoform of the prion protein (PrP(C)) into the pathologic isoform (PrP(Sc)) is the key event in prion diseases. To study the conversion process, an in vitro system based on varying the concentration of low amounts of sodium dodecyl sulfate (SDS) has been employed. In the present study, the conversion of full-length PrP(C) isolated from Chinese hamster ovary cells (CHO-PrP(C)) was examined. CHO-PrP(C) harbors native, posttranslational modifications, including the GPI anchor and two N-linked glyco-sylation sites. The properties of CHO-PrP(C) were compared with those of full-length and N-terminally truncated recombinant PrP. As shown earlier with recombinant PrP (recPrP90-231), transition from a soluble α-helical state as known for native PrP(C) into an aggregated, β-sheet-rich PrP(Sc)-like state could be induced by dilution of SDS. The aggregated state is partially proteinase K (PK)-resistant, exhibiting a cleavage site similar to that found with PrP(Sc). Compared to recPrP (90-231), fibril formation with CHO-PrP(C) requires lower SDS concentrations (0.0075%), and can be drastically accelerated by seeding with PrP(Sc) purified from brain homogenates of terminally sick hamsters. Our results show that recPrP 90-231 and CHO-PrPC behave qualitatively similar but quantitatively different. The in vivo situation can be simulated closer with CHO-PrP(C) because the specific PK cleave site could be shown and the seed-assisted fibrillization was much more efficient. |