Influence of pH on the human prion protein: insights into the early steps of misfolding

Marc W van der Kamp, Valerie Daggett

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

62 Citations (Scopus)

Abstract

Transmissible spongiform encephalopathies, or prion diseases, are caused by misfolding and aggregation of the prion protein PrP. Conversion from the normal cellular form (PrP(C)) or recombinant PrP (recPrP) to a misfolded form is pH-sensitive, in that misfolding and aggregation occur more readily at lower pH. To gain more insight into the influence of pH on the dynamics of PrP and its potential to misfold, we performed extensive molecular-dynamics simulations of the recombinant PrP protein (residues 90-230) in water at three different pH regimes: neutral (or cytoplasmic) pH (∼7.4), middle (or endosomal) pH (∼5), and low pH (
Original languageEnglish
Pages (from-to)2289-98
Number of pages10
JournalBiophysical Journal
Volume99
Issue number7
DOIs
Publication statusPublished - 6 Oct 2010

Bibliographical note

Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Keywords

  • Hydrophobic and Hydrophilic Interactions
  • Protein Structure, Secondary
  • Pliability
  • Computer Simulation
  • Models, Molecular
  • Protein Stability
  • Hydrogen-Ion Concentration
  • Humans
  • Histidine
  • Protein Folding
  • Prions
  • Protein Structure, Quaternary

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