Structural Changes of Membrane-anchored Native PrP(C)

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Aug 2

PMID 18669653

Citations 20

Authors

Kerstin Elfrink

Julian Ollesch

Jan Stohr

Dieter Willbold

Detlev Riesner

Klaus Gerwert

Affiliations

Soon will be listed here.

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.

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