Free Energy and Hidden Barriers of the β-Sheet Structure of Prion Protein

2015 ◽  
Vol 11 (10) ◽  
pp. 5024-5034 ◽  
Author(s):  
S. Alexis Paz ◽  
Cameron F. Abrams
Keyword(s):  
Free Energy ◽  
Prion Protein ◽  
Sheet Structure ◽  
Β Sheet

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.

Rapid Acquisition of β-Sheet Structure in the Prion Protein Prior to Multimer Formation

1998 ◽  
Vol 379 (11) ◽  
Author(s):  
Karin Post ◽  
Martin Pitschke ◽  
Oliver Schäfer ◽  
Holger Wille ◽  
Thomas R. Appel ◽  
...  
Keyword(s):  
Prion Protein ◽  
Rapid Acquisition ◽  
Sheet Structure ◽  
Β Sheet

scholarly journals Most of the structural elements of the globular domain of murine prion protein form fibrils with predominant β-sheet structure

FEBS Letters ◽  
2002 ◽  
Vol 529 (2-3) ◽  
pp. 256-260 ◽  
Author(s):  
Nadège Jamin ◽  
Yves-Marie Coı̈c ◽  
Céline Landon ◽  
Ludmila Ovtracht ◽  
Françoise Baleux ◽  
...  
Keyword(s):  
Prion Protein ◽  
Globular Domain ◽  
Structural Elements ◽  
Sheet Structure ◽  
Β Sheet

On the roles of the alanine and serine in the β-sheet structure of fibroin

2015 ◽  
Vol 197 ◽  
pp. 10-17 ◽  
Author(s):  
Juan Francisco Carrascoza Mayen ◽  
Alexandru Lupan ◽  
Ciprian Cosar ◽  
Attila-Zsolt Kun ◽  
Radu Silaghi-Dumitrescu
Keyword(s):  
Sheet Structure ◽  
Β Sheet

scholarly journals Altered toxicity of the prion protein peptide PrP106–126 carrying the Ala117→Val mutation

2000 ◽  
Vol 346 (3) ◽  
pp. 785-791 ◽  
Author(s):  
David R. BROWN
Keyword(s):  
Point Mutation ◽  
Prion Protein ◽  
Prion Diseases ◽  
Point Mutations ◽  
Human Sequence ◽  
Gene Coding ◽  
Normal Human ◽  
Microtubule Formation ◽  
Β Sheet ◽  
Prion Protein Peptide

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 (PrPC). One particular point mutation A117V (Ala117 → Val) is linked to a variable pathology that usually includes deposition of neurofibrillary tangles. A prion protein peptide carrying this point mutation [PrP106-126(117V)] was generated and compared with a peptide based on the normal human sequence [PrP106-126(117A)]. The inclusion of this point mutation increased the toxicity of PrP106-126 which could be linked to an increased β-sheet content. An assay of microtubule formation in the presence of tau indicated that PrP106-126 decreased the rate of microtubule formation that could be related to the displacement of tau. PrP106-126 carrying the 117 mutation was more efficient at inhibiting microtubule formation. These results suggest a possible mechanism of toxicity for protein carrying this mutation via destabilization of the cytoskeleton and deposition of tau in filaments, as observed in GSS.

Effect of curcumin on amyloidogenic property of molten globule-like intermediate state of 2,5-diketo-d-gluconate reductase A

2009 ◽  
Vol 390 (10) ◽  
Author(s):  
Nandini Sarkar ◽  
Abhay Narain Singh ◽  
Vikash Kumar Dubey
Keyword(s):  
Protein Concentration ◽  
Molten Globule ◽  
Molar Ratio ◽  
Amyloid Formation ◽  
Molten Globule State ◽  
Force Microscopy ◽  
Atomic Force ◽  
Sheet Structure ◽  
Amyloid Diseases ◽  
Β Sheet

Abstract We identified a molten globule-like intermediate of 2,5-diketo-d-gluconate reductase A (DKGR) at pH 2.5, which has a prominent β-sheet structure. The molten globule state of the protein shows amyloidogenic property >50 μm protein concentration. Interestingly, a 1:1 molar ratio of curcumin prevents amyloid formation as shown by the Thioflavin-T assay and atomic force microscopy. To the best of our knowledge, this is the first report on amyloid formation by an (α/β)8-barrel protein. The results presented here indicate that the molten globule state has an important role in amyloid formation and potential application of curcumin in protein biotechnology as well as therapeutics against amyloid diseases.

COMPARING FOLDING MECHANISMS OF DIFFERENT PRION PROTEINS BY Gō MODEL

2013 ◽  
Vol 12 (08) ◽  
pp. 1341004
Author(s):  
XUE WU ◽  
TING FU ◽  
ZHI-LONG XIU ◽  
LIU YIN ◽  
JIN-GUANG WANG ◽  
...  
Keyword(s):  
Free Energy ◽  
Prion Protein ◽  
Energy Barrier ◽  
Prion Proteins ◽  
Coarse Grained ◽  
Transmissible Spongiform Encephalopathies ◽  
Free Energy Barrier ◽  
Spongiform Encephalopathies ◽  
Go Model ◽  
Folding Free Energy

Prions are associated with neurodegenerative diseases induced by transmissible spongiform encephalopathies. The infectious scrapie form is referred to as PrP Sc , which has conformational change from normal prion with predominant α-helical conformation to the abnormal PrP Sc that is rich in β-sheet content. Neurodegenerative diseases have been found from both human and bovine sources, but there are no reports about infected by transmissible spongiform encephalopathies from rabbit, canine and horse sources. Here we used coarse-grained Gō model to compare the difference among human, bovine, rabbit, canine, and horse normal (cellular) prion proteins. The denatured state of normal prion has relation with the conversion from normal to abnormal prion protein, so we used all-atom Gō model to investigate the folding pathway and energy landscape for human prion protein. Through using coarse-grained Gō model, the cooperativity of the five prion proteins was characterized in terms of calorimetric criterion, sigmoidal transition, and free-energy profile. The rabbit and horse prion proteins have higher folding free-energy barrier and cooperativity, and canine prion protein has slightly higher folding free-energy barrier comparing with human and bovine prion proteins. The results from all-atom Gō model confirmed the validity of C α-Gō model. The correlations of our results with previous experimental and theoretical researches were discussed.

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