TY  - JOUR
AU  - Elfrink, K.
AU  - Ollesch, J.
AU  - Stoehr, J.
AU  - Willbold, D.
AU  - Riesner, D.
AU  - Gerwert, K.
TI  - Structural changes of membrane-anchored native PrPc
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 105
SN  - 0027-8424
CY  - Washington, DC
PB  - Academy
M1  - PreJuSER-340
SP  - 10815 - 10819
PY  - 2008
N1  - Record converted from VDB: 12.11.2012
AB  - 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.
KW  - Animals
KW  - Cricetinae
KW  - Membrane Proteins: genetics
KW  - Mesocricetus
KW  - Models, Molecular
KW  - PrPC Proteins: genetics
KW  - Protein Conformation
KW  - Protein Folding
KW  - Spectroscopy, Fourier Transform Infrared
KW  - Membrane Proteins (NLM Chemicals)
KW  - PrPC Proteins (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:18669653
C2  - pmc:PMC2504809
UR  - <Go to ISI:>//WOS:000258308500036
DO  - DOI:10.1073/pnas.0804721105
UR  - https://juser.fz-juelich.de/record/340
ER  -