Strain-dependent Differences in β-Sheet Conformations of Abnormal Prion Protein
نویسندگان
چکیده
منابع مشابه
Polymorphism at 129 dictates metastable conformations of the human prion protein N-terminal β-sheet.
We study the thermodynamic stability of the native state of the human prion protein using a new free-energy method, replica-exchange on-the-fly parameterization. This method is designed to overcome hidden-variable sampling limitations to yield nearly error-free free-energy profiles along a conformational coordinate. We confirm that all four (M129V, D178N) polymorphs have a ground-state conforma...
متن کاملThe cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication.
Formation of aberrant protein conformers is a common pathological denominator of different neurodegenerative disorders, such as Alzheimer's disease or prion diseases. Moreover, increasing evidence indicates that soluble oligomers are associated with early pathological alterations and that oligomeric assemblies of different disease-associated proteins may share common structural features. Previo...
متن کاملDeadly Conformations—Protein Misfolding in Prion Disease
and progressive dementia, occurring after age 40, associated , as in kuru, with plaques in the brain of affected * Department of Genetics and Howard Hughes Medical Institute individuals (Gerstmann et al., 1936). Multiple affected family members were observed, in a pattern indicating Yale University School of Medicine New Haven, Connecticut 06510 autosomal-dominant inheritance. Similar genetic t...
متن کاملPrion strain-dependent differences in conversion of mutant prion proteins in cell culture.
Although the protein-only hypothesis proposes that it is the conformation of abnormal prion protein (PrP(Sc)) that determines strain diversity, the molecular basis of strains remains to be elucidated. In the present study, we generated a series of mutations in the normal prion protein (PrP(C)) in which a single glutamine residue was replaced with a basic amino acid and compared their abilities ...
متن کاملStrain-dependent profile of misfolded prion protein aggregates
Prions are composed of the misfolded prion protein (PrP(Sc)) organized in a variety of aggregates. An important question in the prion field has been to determine the identity of functional PrP(Sc) aggregates. In this study, we used equilibrium sedimentation in sucrose density gradients to separate PrP(Sc) aggregates from three hamster prion strains (Hyper, Drowsy, SSLOW) subjected to minimal ma...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Journal of Biological Chemistry
سال: 1998
ISSN: 0021-9258
DOI: 10.1074/jbc.273.48.32230