Related Experiment Video
Updated: Jun 16, 2026

Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Fragment molecular orbital calculations reveal that the E200K mutation markedly alters local structural stability in
Koji Hasegawa1, Shirou Mohri, Takashi Yokoyama
1AdvanceSoft Corporation, Akasaka, Tokyo, Japan. khasegawa@advancesoft.jp
Abstract:
The E200K mutation of the human prion protein (PrP) is known to cause familial Creutzfeldt-Jakob disease. In order to elucidate the effects of the mutation on the local structural stability of PrP, we performed ab initio fragment molecular orbital calculations for the wild-type human PrP and the E200K variant modeled under neutral and mild acidic conditions. The calculations revealed that this substitution markedly altered the intramolecular interactions in the PrP, suggesting that the local structural instabilities induced by the E200K mutation might cause initial denaturation of the PrP and its subsequent conversion to a pathogenic form. This work presents a new approach for quantitatively elucidating structural instabilities in proteins that cause misfolding diseases.
Related Concept Videos
Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Mutations
Mutations
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Point and Frameshift Mutations
Mutations in Microorganisms
Molecular Chaperones and Protein Folding
The...

