Structural changes of membrane-anchored native PrPc

Elfrink, K.; Ollesch, J.; Riesner, D.; Gerwert, K.; Stoehr, J.; Willbold, D.

doi:10.1073/pnas.0804721105

Journal Article

Structural changes of membrane-anchored native PrPc

Elfrink, K. ; Ollesch, J. ; Stoehr, J. ; Willbold, D.FZJ* ; Riesner, D. ; Gerwert, K.

2008
Academy Washington, DC

Proceedings of the National Academy of Sciences of the United States of America 105, 10815 - 10819 (2008) [10.1073/pnas.0804721105]

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Please use a persistent id in citations: doi:10.1073/pnas.0804721105

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.

Keyword(s): Animals (MeSH) ; Cricetinae (MeSH) ; Membrane Proteins: genetics (MeSH) ; Mesocricetus (MeSH) ; Models, Molecular (MeSH) ; PrPC Proteins: genetics (MeSH) ; Protein Conformation (MeSH) ; Protein Folding (MeSH) ; Spectroscopy, Fourier Transform Infrared (MeSH) ; Membrane Proteins ; PrPC Proteins ; J ; FTIR (auto) ; membrane anchoring (auto) ; prion protein (auto) ; protein aggregation (auto) ; secondary structure (auto)