Structural changes of membrane-anchored native PrP(C)

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...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2008-08, Vol.105 (31), p.10815-10819
Main Authors: Elfrink, Kerstin, Ollesch, Julian, Stöhr, Jan, Willbold, Dieter, Riesner, Detlev, Gerwert, Klaus
Format: Article
Language:English
Subjects:
Animals
Cricetinae
Membrane Proteins - genetics
Mesocricetus
Models, Molecular
Protein Conformation
Protein Folding
PrPC Proteins - genetics
Spectroscopy, Fourier Transform Infrared
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container_issue 31
container_start_page 10815
container_title Proceedings of the National Academy of Sciences - PNAS
container_volume 105
creator Elfrink, Kerstin
Ollesch, Julian
Stöhr, Jan
Willbold, Dieter
Riesner, Detlev
Gerwert, Klaus
description 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.
doi_str_mv 10.1073/pnas.0804721105
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subjects Animals
Cricetinae
Membrane Proteins - genetics
Mesocricetus
Models, Molecular
Protein Conformation
Protein Folding
PrPC Proteins - genetics
Spectroscopy, Fourier Transform Infrared
title Structural changes of membrane-anchored native PrP(C)
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