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

Marc W van der Kamp; Valerie Daggett

doi:10.1016/j.bpj.2010.07.063

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

Marc W van der Kamp
, Valerie Daggett

School of Chemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

79 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 language	English
Pages (from-to)	2289-98
Number of pages	10
Journal	Biophysical Journal
Volume	99
Issue number	7
DOIs	https://doi.org/10.1016/j.bpj.2010.07.063
Publication status	Published - 6 Oct 2010

Bibliographical note

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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title = "Influence of pH on the human prion protein: insights into the early steps of misfolding",

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 (",

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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year = "2010",

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T1 - Influence of pH on the human prion protein

T2 - insights into the early steps of misfolding

AU - van der Kamp, Marc W

AU - Daggett, Valerie

PY - 2010/10/6

Y1 - 2010/10/6

N2 - 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 (

AB - 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 (

KW - Hydrophobic and Hydrophilic Interactions

KW - Protein Structure, Secondary

KW - Pliability

KW - Computer Simulation

KW - Models, Molecular

KW - Protein Stability

KW - Hydrogen-Ion Concentration

KW - Humans

KW - Histidine

KW - Protein Folding

KW - Prions

KW - Protein Structure, Quaternary

U2 - 10.1016/j.bpj.2010.07.063

DO - 10.1016/j.bpj.2010.07.063

M3 - Article (Academic Journal)

C2 - 20923664

SN - 1542-0086

VL - 99

SP - 2289

EP - 2298

JO - Biophysical Journal

JF - Biophysical Journal

IS - 7

ER -

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

Abstract

Bibliographical note

Keywords

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