Structural changes of membrane-anchored native PrP?^sup C

Misfolding and subsequent aggregation of endogeneous proteins constitute essential steps in many human disorders, including Alzheimer and prion diseases. In most prion protein-folding studies, the posttranslational modifications, the lipid anchor in particular, were lacking. Here, we studied a fully...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-08, Vol.105 (31), p.10815
Main Authors: Elfrink, Kerstin, Ollesch, Julian, Stöhr, Jan, Willbold, Dieter, Riesner, Detlev, Gerwert, Klaus
Format: Article
Language:English
Subjects:
Alzheimer's disease
Changes
Membranes
Prions
Protein folding
Studies
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Summary:Misfolding and subsequent aggregation of endogeneous proteins constitute essential steps in many human disorders, including Alzheimer and prion diseases. In most prion protein-folding studies, the posttranslational modifications, the lipid anchor in particular, were lacking. Here, we studied a fully posttranslationally modified cellular prion protein, carrying two N-glycosylations and the natural GPI anchor. We used time-resolved FTIR to study the prion protein secondary structure changes when binding to a raft-like lipid membrane via its GPI anchor. We observed that membrane anchoring above a threshold concentration induced refolding of the prion protein to intermolecular β-sheets. Such transition is not observed in solution and is membrane specific. Excessive membrane anchoring, analyzed with molecular sensitivity, is thought to be a crucial event in the development of prion diseases. [PUBLICATION ABSTRACT]
ISSN:0027-8424
1091-6490