Molecular Dynamics Simulations of Prion Proteins - Effect of Ala→Val mutation-
نویسندگان
چکیده
We investigated the conformational change in the human prion protein owing to an Ala→Val mutation by using molecular dynamics simulations. This mutation is related to Gerstmann-Sträussler-Sheinker disease, one of the familial prion diseases. Five prion protein structures were simulated in the periodic or non-periodic system. The results of molecular dynamics calculations indicated that the globular domains of wild-type structures (109-228 and 90-228) were stable. In contrast, the globular domains of mutant structures (109-228 and 90-228) were sensitive to the N-terminal region possessing the Ala→Val mutation, and the β-sheet regions were increased.
منابع مشابه
Introducing critical residues in the human prion protein and its Asp 178 Asn mutant by molecular dynamics simulation
The molecular dynamics (MD) simulation method is used to assess structural details for humanprion protein (hereafter PrPN) and its Asp178 Asn mutant (hereafter PrPm) which causes fatalfamilial insomnia disease. The results reveal that the flexibility and instability increase in PrPmcould be related to specific amino acids exposed to the solvent. Solvation free energy of PrPm is 20kjmot1nni2 mor...
متن کاملMolecular dynamics as an approach to study prion protein misfolding and the effect of pathogenic mutations.
Computer simulation of protein dynamics offers unique high-resolution information that complements experiment. Using experimentally derived structures of the natively folded prion protein (PrP), physically realistic dynamics and conformational changes can be simulated, including the initial steps of misfolding. By introducing mutations in silico, the effect of pathogenic mutations on PrP confor...
متن کاملOne gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures.
Fatal familial insomnia (FFI) and Creutzfeldt-Jakob disease (CJD) are associated to the same mutation at codon 178 but differentiate into clinicopathologically distinct diseases determined by this mutation and a naturally occurring methionine-valine polymorphism at codon 129 of the prion protein gene. It has been suggested that the clinical and pathological difference between FFI and CJD is cau...
متن کاملEffects of Dimethyl Sulfoxide and Mutations on the Folding of Abeta(25-35) Peptide: Molecular Dynamics Simulations
The 25-35 fragment of the amyloid β (Aβ) peptide is a naturally occurring proteolytic by-product of its larger parent molecule that retains the amyloid characteristics and toxicity of the full length parent molecule. Aggregation of this peptide occurs rapidly in aqueous solutions and thus characterization of its folding process is very difficult. In the present study, early stages of Aβ(25–35) ...
متن کاملAltered toxicity of the prion protein peptide PrP106-126 carrying the Ala(117)-->Val mutation.
The inherited prion diseases such as Gerstmann-Sträussler-Scheinker syndrome (GSS) are linked to point mutations in the gene coding for the cellular isoform of the prion protein (PrP(C)). One particular point mutation A117V (Ala(117)-->Val) is linked to a variable pathology that usually includes deposition of neurofibrillary tangles. A prion protein peptide carrying this point mutation [PrP106-...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره شماره
صفحات -
تاریخ انتشار 2003