Simulations of membrane-bound diglycosylated human prion protein reveal potential protective mechanisms against misfolding

Chin Jung Cheng, Heidi Koldsø, Marc Van der Kamp, Birgit Schiøtt, Valerie Daggett

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
229 Downloads (Pure)

Abstract

Prion diseases are associated with the misfolding of the prion protein (PrP) from its normal cellular form (PrPC) to its infectious scrapie form (PrPSc). Posttranslational modifications of PrP in vivo can play an important role in modulating the process of misfolding. To gain more insight into the effects of posttranslational modifications on PrP structure and dynamics and to test the hypothesis that such modifications can interact with the protein, we have performed molecular dynamics simulations of diglycosylated human PrPC bound to a lipid bilayer via a glycophosphatidylinositol anchor. Multiple simulations were performed at three different pH ranges to explore pH effects on structure and dynamics. In contrast to simulations of protein-only PrPC, no large effects were observed upon lowering the pH of the system. The protein tilted toward the membrane surface in all of the simulations and the putative PrPSc oligomerization sites became inaccessible, thereby offering a possible protective mechanism against PrPSc-induced misfolding of PrPC.
Original languageEnglish
Pages (from-to)171-182
Number of pages13
JournalJournal of Neurochemistry
Volume142
Issue number1
Early online date22 May 2017
DOIs
Publication statusPublished - Jul 2017

Keywords

  • Prion protein misfolding
  • Membrane simulation
  • Molecular dynamics

Fingerprint Dive into the research topics of 'Simulations of membrane-bound diglycosylated human prion protein reveal potential protective mechanisms against misfolding'. Together they form a unique fingerprint.

Cite this