ArticleJournal of molecular biology2010
Pathogenic mutations in the hydrophobic core of the human prion protein can promote structural instability and misfolding.
Article in Journal of molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 110 citations in OpenAlex.
- Deep-learning structure elucidation from single-mutant deep mutational scanning.Nature communications · 2025Article
- The role of α-sheet structure in amyloidogenesis: characterization and implications.Open biology · 2022Review
- Multi-eGO: An in silico lens to look into protein aggregation kinetics at atomic resolution.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural and Functional Differences between Homologous Bacterial Ribonucleases.International journal of molecular sciences · 2022Article
- A seven-residue deletion in PrP leads to generation of a spontaneous prion formed from C-terminal C1 fragment of PrP.The Journal of biological chemistry · 2020Article
- Structural insight into conformational change in prion protein by breakage of electrostatic network around H187 due to its protonation.Scientific reports · 2019Article
- Atomic insights into the effects of pathological mutants through the disruption of hydrophobic core in the prion protein.Scientific reports · 2019Article
- Detecting early stage structural changes in wild type, pathogenic and non-pathogenic prion variants using Markov state model.RSC advances · 2019Article
- Structural Determinants of the Prion Protein N-Terminus and Its Adducts with Copper Ions.International journal of molecular sciences · 2018Review
- Effects of pH and aggregation in the human prion conversion into scrapie form: a study using molecular dynamics with excited normal modes.European biophysics journal : EBJ · 2018Article
- Characterization of mutations inNeuropsychiatric disease and treatment · 2018Review
- Simulations of membrane-bound diglycosylated human prion protein reveal potential protective mechanisms against misfolding.Journal of neurochemistry · 2017Article
- Interplay of buried histidine protonation and protein stability in prion misfolding.Scientific reports · 2017Article
- Detection of prion seeding activity in the olfactory mucosa of patients with Fatal Familial Insomnia.Scientific reports · 2017Article
- Prion diseases: immunotargets and therapy.ImmunoTargets and therapy · 2016Review
- Article
- Molecular Dynamics Simulations of the Temperature Induced Unfolding of Crambin Follow the Arrhenius Equation.F1000Research · 2015Article
- Global human frequencies of predicted nuclear pathogenic variants and the role played by protein hydrophobicity in pathogenicity potential.Scientific reports · 2014Article
- Heparin binding confers prion stability and impairs its aggregation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Structural and dynamic properties of the human prion protein.Biophysical journal · 2014Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Transmissible spongiform encephalopathies, or prion diseases, are caused by misfolding and aggregation of the prion protein PrP. These diseases can be hereditary in humans and four of the many disease-associated missense mutants of PrP are in the hydrophobic core: V180I, F198S, V203I and V210I. The T183A mutation is related to the hydrophobic core mutants as it is close to the hydrophobic core and known to cause instability. We used extensive molecular dynamics simulations of these five PrP mutants to compare their dynamics and conformations to those of the wild type PrP. The simulations highlight the changes that occur upon introduction of mutations and help to rationalize experimental findings. Changes can occur around the mutation site, but they can also be propagated over long distances. In particular, the F198S and T183A mutations lead to increased flexibility in parts of the structure that are normally stable, and the short β-sheet moves away from the rest of the protein. Mutations V180I, V210I and, to a lesser extent, V203I cause changes similar to those observed upon lowering the pH, which has been linked to misfolding. Early misfolding is observed in one V180I simulation. Overall, mutations in the hydrophobic core have a significant effect on the dynamics and stability of PrP, including the propensity to misfold, which helps to explain their role in the development of familial prion diseases.
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