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Updated: Jun 8, 2026

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Exposure of hydrophobic core in human prion protein pathogenic mutant H187R
1Pennsylvania State University at Mont Alto 1 Campus Drive, Mont Alto, Pennsylvania 17237, USA. luz4@psu.edu
Abstract:
Pathogenesis studies have revealed that H187R mutation of human prion protein (huPrP) is related to GSS type of TSE diseases. Its pathogenic mechanism is still unclear. We here studied the globular domain of this mutant protein by molecular dynamics simulations. Compared to the wide-type protein, the mutant has similar dynamics and stability profiles in our simulation. Conformational rearrangements are concentrated around the mutation site, due to the introduction the positively charged side chain of Arg187. The strong electrostatic repulsion between Arg156 and Arg187 drives both side chains away from their original positions, leaving its hydrophobic core to be solvent accessible. Such a unfavorable conformational change may destabilize the mutant protein and make it more susceptible to unfolding.
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