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 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.
Elfrink
Kerstin
K
Institut fuer Physikalische Biologie, Heinrich-Heine-Universitaet Duesseldorf, Universitaetsstrasse 1, 40225 Duesseldorf, Germany.
Ollesch
Julian
J
Stöhr
Jan
J
Willbold
Dieter
D
Riesner
Detlev
D
Gerwert
Klaus
K
D000818:Animals; D006224:Cricetinae; D008565:Membrane Proteins / Q000235:genetics*; D008647:Mesocricetus; D008958:Models, Molecular; D018621:PrPC Proteins / Q000235:genetics*; D011487:Protein Conformation; D017510:Protein Folding; D017550:Spectroscopy, Fourier Transform Infrared
D008565:Membrane Proteins; D018621:PrPC Proteins