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Structural changes of membrane-anchored native PrP(C).

ABSTRACT: Misfolding and subsequent aggregation of endogenous 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 beta-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.

SUBMITTER: Elfrink K

PROVIDER: S-EPMC2504809 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Structural changes of membrane-anchored native PrP(C).

Elfrink Kerstin K Ollesch Julian J Stöhr Jan J Willbold Dieter D Riesner Detlev D Gerwert Klaus K

Proceedings of the National Academy of Sciences of the United States of America 20080731 31

Misfolding and subsequent aggregation of endogenous 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 bi ...[more]

PMID: 18669653

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