Human prion protein: exploring the thermodynamic stability and structural dynamics of its pathogenic mutants

2021 ◽  
pp. 1-17
Author(s):  
Puspita Halder ◽  
Pralay Mitra
Keyword(s):  
Prion Protein ◽  
Structural Dynamics ◽  
Thermodynamic Stability ◽  
Human Prion Protein

scholarly journals Atypical Effect of Salts on the Thermodynamic Stability of Human Prion Protein

2003 ◽  
Vol 278 (25) ◽  
pp. 22187-22192 ◽  
Author(s):  
Adrian C. Apetri ◽  
Witold K. Surewicz
Keyword(s):  
Prion Protein ◽  
Thermodynamic Stability ◽  
Human Prion Protein

scholarly journals Polymorphism at 129 dictates metastable conformations of the human prion protein N-terminal β-sheet

2017 ◽  
Vol 8 (2) ◽  
pp. 1225-1232 ◽  
Author(s):  
S. Alexis Paz ◽  
Eric Vanden-Eijnden ◽  
Cameron F. Abrams
Keyword(s):  
Free Energy ◽  
Prion Protein ◽  
Thermodynamic Stability ◽  
Energy Method ◽  
Replica Exchange ◽  
Native State ◽  
Human Prion Protein ◽  
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.

scholarly journals Familial Mutations and the Thermodynamic Stability of the Recombinant Human Prion Protein

1998 ◽  
Vol 273 (47) ◽  
pp. 31048-31052 ◽  
Author(s):  
Wieslaw Swietnicki ◽  
Robert B. Petersen ◽  
Pierluigi Gambetti ◽  
Witold K. Surewicz
Keyword(s):  
Prion Protein ◽  
Thermodynamic Stability ◽  
Human Prion Protein

scholarly journals The polyphenolic phytoalexin polydatin inhibits amyloid aggregation of recombinant human prion protein

RSC Advances ◽  
2021 ◽  
Vol 11 (42) ◽  
pp. 25901-25911
Author(s):  
Preeti Rana Sirohi ◽  
Anchala Kumari ◽  
Nikita Admane ◽  
Pallavi Somvanshi ◽  
Abhinav Grover
Keyword(s):  
Prion Protein ◽  
Amyloid Aggregation ◽  
Drug Lead ◽  
Human Prion Protein

Polydatin is found to be a pharmacologically-significant scaffold that can bind to the rPrPres repertoire and inhibit its conversion to the highly infectious and neurotoxic PrPSc-like form, thus acting like a promising anti-prion drug lead.

scholarly journals Sensitive protein misfolding cyclic amplification of sporadic Creutzfeldt–Jakob disease prions is strongly seed and substrate dependent

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maxime Bélondrade ◽  
Simon Nicot ◽  
Charly Mayran ◽  
Lilian Bruyere-Ostells ◽  
Florian Almela ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Misfolding ◽  
Protein Misfolding Cyclic Amplification ◽  
Bank Voles ◽  
Substrate Dependence ◽  
Brain Extracts ◽  
Jakob Disease ◽  
Human Prion Protein

AbstractUnlike variant Creutzfeldt–Jakob disease prions, sporadic Creutzfeldt–Jakob disease prions have been shown to be difficult to amplify in vitro by protein misfolding cyclic amplification (PMCA). We assessed PMCA of pathological prion protein (PrPTSE) from 14 human sCJD brain samples in 3 substrates: 2 from transgenic mice expressing human prion protein (PrP) with either methionine (M) or valine (V) at position 129, and 1 from bank voles. Brain extracts representing the 5 major clinicopathological sCJD subtypes (MM1/MV1, MM2, MV2, VV1, and VV2) all triggered seeded PrPTSE amplification during serial PMCA with strong seed- and substrate-dependence. Remarkably, bank vole PrP substrate allowed the propagation of all sCJD subtypes with preservation of the initial molecular PrPTSE type. In contrast, PMCA in human PrP substrates was accompanied by a PrPTSE molecular shift during heterologous (M/V129) PMCA reactions, with increased permissiveness of V129 PrP substrate to in vitro sCJD prion amplification compared to M129 PrP substrate. Combining PMCA amplification sensitivities with PrPTSE electrophoretic profiles obtained in the different substrates confirmed the classification of 4 distinct major sCJD prion strains (M1, M2, V1, and V2). Finally, the level of sensitivity required to detect VV2 sCJD prions in cerebrospinal fluid was achieved.

scholarly journals Backbone NMR assignments of the C-terminal domain of the human prion protein and its disease‐associated T183A variant

2021 ◽  
Vol 15 (1) ◽  
pp. 193-196
Author(s):  
Máximo Sanz-Hernández ◽  
Alfonso De Simone
Keyword(s):  
Prion Protein ◽  
Nmr Assignments ◽  
Chemical Shifts ◽  
Prion Diseases ◽  
Random Coil ◽  
Transmissible Spongiform Encephalopathies ◽  
Globular Domain ◽  
Structural Elements ◽  
Spongiform Encephalopathies ◽  
Human Prion Protein

AbstractTransmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative disorders associated with the misfolding and aggregation of the human prion protein (huPrP). Despite efforts into investigating the process of huPrP aggregation, the mechanisms triggering its misfolding remain elusive. A number of TSE-associated mutations of huPrP have been identified, but their role at the onset and progression of prion diseases is unclear. Here we report the NMR assignments of the C-terminal globular domain of the wild type huPrP and the pathological mutant T183A. The differences in chemical shifts between the two variants reveal conformational alterations in some structural elements of the mutant, whereas the analyses of secondary shifts and random coil index provide indications on the putative mechanisms of misfolding of T183A huPrP.

scholarly journals Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical bovine spongiform encephalopathy

2013 ◽  
Vol 94 (12) ◽  
pp. 2819-2827 ◽  
Author(s):  
Rona Wilson ◽  
Karen Dobie ◽  
Nora Hunter ◽  
Cristina Casalone ◽  
Thierry Baron ◽  
...  
Keyword(s):  
Human Health ◽  
Bovine Spongiform Encephalopathy ◽  
Prion Protein ◽  
Disease Transmission ◽  
Large Scale ◽  
Single Agent ◽  
Diagnostic Methods ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathy ◽  
Human Prion Protein

The transmission of bovine spongiform encephalopathy (BSE) to humans, leading to variant Creutzfeldt–Jakob disease has demonstrated that cattle transmissible spongiform encephalopathies (TSEs) can pose a risk to human health. Until recently, TSE disease in cattle was thought to be caused by a single agent strain, BSE, also known as classical BSE, or BSE-C. However, due to the initiation of a large-scale surveillance programme throughout Europe, two atypical BSE strains, bovine amyloidotic spongiform encephalopathy (BASE, also named BSE-L) and BSE-H have since been discovered. To model the risk to human health, we previously inoculated these two forms of atypical BSE (BASE and BSE-H) into gene-targeted transgenic (Tg) mice expressing the human prion protein (PrP) (HuTg) but were unable to detect any signs of TSE pathology in these mice. However, despite the absence of TSE pathology, upon subpassage of some BASE-challenged HuTg mice, a TSE was observed in recipient gene-targeted bovine PrP Tg (Bov6) mice but not in HuTg mice. Disease transmission from apparently healthy individuals indicates the presence of subclinical BASE infection in mice expressing human PrP that cannot be identified by current diagnostic methods. However, due to the lack of transmission to HuTg mice on subpassage, the efficiency of mouse-to-mouse transmission of BASE appears to be low when mice express human rather than bovine PrP.

Sign in / Sign up

Export Citation Format

Share Document