Molecular Dynamics Simulation of Dimeric and Monomeric Forms of Human Prion Protein: Insight into Dynamics and Properties

A central theme in prion protein research is the detection of the process that underlies the conformational transition from the normal cellular prion form (PrP C) to its pathogenic isoform (PrP Sc). Although the three-dimensional structures of monomeric and dimeric human prion protein (HuPrP) have b...

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Bibliographic Details
Published in:Biophysical journal 2003-08, Vol.85 (2), p.1176-1185
Main Authors: Sekijima, Masakazu, Motono, Chie, Yamasaki, Satoshi, Kaneko, Kiyotoshi, Akiyama, Yutaka
Format: Article
Language:English
Subjects:
Binding Sites
Biopolymers - chemistry
Computer Simulation
Dimerization
Humans
Macromolecular Substances
Models, Molecular
molecular dynamics
Motion
Prions
Prions - chemistry
Protein Binding
Protein Conformation
Protein Structure, Secondary
Protein Structure, Tertiary
Proteins
PrPC Proteins - chemistry
PrPSc Proteins - chemistry
Simulation
Spectrum analysis
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Summary:A central theme in prion protein research is the detection of the process that underlies the conformational transition from the normal cellular prion form (PrP C) to its pathogenic isoform (PrP Sc). Although the three-dimensional structures of monomeric and dimeric human prion protein (HuPrP) have been revealed by NMR spectroscopy and x-ray crystallography, the process underlying the conformational change from PrP C to PrP Sc and the dynamics and functions of PrP C remain unknown. The dimeric form is thought to play an important role in the conformational transition. In this study, we performed molecular dynamics (MD) simulations on monomeric and dimeric HuPrP at 300 K and 500 K for 10 ns to investigate the differences in the properties of the monomer and the dimer from the perspective of dynamic and structural behaviors. Simulations were also undertaken with Asp178Asn and acidic pH, which is known as a disease-associated factor. Our results indicate that the dynamics of the dimer and monomer were similar (e.g., denaturation of helices and elongation of the β-sheet). However, additional secondary structure elements formed in the dimer might result in showing the differences in dynamics and properties between the monomer and dimer (e.g., the greater retention of dimeric than monomeric tertiary structure).
ISSN:0006-3495
1542-0086
DOI:10.1016/S0006-3495(03)74553-6