%0 Journal Article
%A Elfrink, K.
%A Ollesch, J.
%A Stoehr, J.
%A Willbold, D.
%A Riesner, D.
%A Gerwert, K.
%T Structural changes of membrane-anchored native PrPc
%J Proceedings of the National Academy of Sciences of the United States of America
%V 105
%@ 0027-8424
%C Washington, DC
%I Academy
%M PreJuSER-340
%P 10815 - 10819
%D 2008
%Z Record converted from VDB: 12.11.2012
%X 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.
%K Animals
%K Cricetinae
%K Membrane Proteins: genetics
%K Mesocricetus
%K Models, Molecular
%K PrPC Proteins: genetics
%K Protein Conformation
%K Protein Folding
%K Spectroscopy, Fourier Transform Infrared
%K Membrane Proteins (NLM Chemicals)
%K PrPC Proteins (NLM Chemicals)
%K J (WoSType)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:18669653
%2 pmc:PMC2504809
%U <Go to ISI:>//WOS:000258308500036
%R 10.1073/pnas.0804721105
%U https://juser.fz-juelich.de/record/340