Development of the Structural Core and of Conformational Heterogeneity during the Conversion of Oligomers of the Mouse Prion Protein to Worm-like Amyloid Fibrils

2012 ◽  
Vol 423 (2) ◽  
pp. 217-231 ◽  
Author(s):  
Jogender Singh ◽  
A.T. Sabareesan ◽  
M.K. Mathew ◽  
Jayant B. Udgaonkar
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Conformational Heterogeneity

scholarly journals Temperature-Dependent Structural Variability of Prion Protein Amyloid Fibrils

2021 ◽  
Vol 22 (10) ◽  
pp. 5075
Author(s):  
Mantas Ziaunys ◽  
Andrius Sakalauskas ◽  
Kamile Mikalauskaite ◽  
Ruta Snieckute ◽  
Vytautas Smirnovas
Keyword(s):  
Protein Aggregation ◽  
Prion Protein ◽  
Amyloid Fibrils ◽  
Prion Diseases ◽  
Morphological Properties ◽  
Large Sample Size ◽  
Structural Variations ◽  
Temperature Dependent ◽  
Protein Fibrils ◽  
Propagation Properties

Prion protein aggregation into amyloid fibrils is associated with the onset and progression of prion diseases—a group of neurodegenerative amyloidoses. The process of such aggregate formation is still not fully understood, especially regarding their polymorphism, an event where the same type of protein forms multiple, conformationally and morphologically distinct structures. Considering that such structural variations can greatly complicate the search for potential antiamyloid compounds, either by having specific propagation properties or stability, it is important to better understand this aggregation event. We have recently reported the ability of prion protein fibrils to obtain at least two distinct conformations under identical conditions, which raised the question if this occurrence is tied to only certain environmental conditions. In this work, we examined a large sample size of prion protein aggregation reactions under a range of temperatures and analyzed the resulting fibril dye-binding, secondary structure and morphological properties. We show that all temperature conditions lead to the formation of more than one fibril type and that this variability may depend on the state of the initial prion protein molecules.

scholarly journals 13C and 15N chemical shift assignments of mammalian Y145Stop prion protein amyloid fibrils

2016 ◽  
Vol 11 (1) ◽  
pp. 75-80 ◽  
Author(s):  
Theint Theint ◽  
Philippe S. Nadaud ◽  
Krystyna Surewicz ◽  
Witold K. Surewicz ◽  
Christopher P. Jaroniec
Keyword(s):  
Chemical Shift ◽  
Prion Protein ◽  
Amyloid Fibrils ◽  
Chemical Shift Assignments

scholarly journals Self-Replication of Prion Protein Fragment 89-230 Amyloid Fibrils Accelerated by Prion Protein Fragment 107-143 Aggregates

2020 ◽  
Vol 21 (19) ◽  
pp. 7410
Author(s):  
Tomas Sneideris ◽  
Mantas Ziaunys ◽  
Brett K.-Y. Chu ◽  
Rita P.-Y. Chen ◽  
Vytautas Smirnovas
Keyword(s):  
Prion Protein ◽  
Disease Transmission ◽  
Amyloid Fibrils ◽  
The Self ◽  
Transmissible Spongiform Encephalopathies ◽  
Protein Fragment ◽  
Spongiform Encephalopathies ◽  
Amyloid Fibril Formation ◽  
Amyloid Aggregates ◽  
Self Replication

Prion protein amyloid aggregates are associated with infectious neurodegenerative diseases, known as transmissible spongiform encephalopathies. Self-replication of amyloid structures by refolding of native protein molecules is the probable mechanism of disease transmission. Amyloid fibril formation and self-replication can be affected by many different factors, including other amyloid proteins and peptides. Mouse prion protein fragments 107-143 (PrP(107-143)) and 89-230 (PrP(89-230)) can form amyloid fibrils. β-sheet core in PrP(89-230) amyloid fibrils is limited to residues ∼160–220 with unstructured N-terminus. We employed chemical kinetics tools, atomic force microscopy and Fourier-transform infrared spectroscopy, to investigate the effects of mouse prion protein fragment 107-143 fibrils on the aggregation of PrP(89-230). The data suggest that amyloid aggregates of a short prion-derived peptide are not able to seed PrP(89-230) aggregation; however, they accelerate the self-replication of PrP(89-230) amyloid fibrils. We conclude that PrP(107-143) fibrils could facilitate the self-replication of PrP(89-230) amyloid fibrils in several possible ways, and that this process deserves more attention as it may play an important role in amyloid propagation.

scholarly journals The uptake of tau amyloid fibrils is facilitated by the cellular prion protein and hampers prion propagation in cultured cells

2020 ◽  
Vol 155 (5) ◽  
pp. 577-591 ◽  
Author(s):  
Elena De Cecco ◽  
Luigi Celauro ◽  
Silvia Vanni ◽  
Micaela Grandolfo ◽  
Edoardo Bistaffa ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Cultured Cells ◽  
Cellular Prion Protein ◽  
Prion Propagation

Prion Protein Aggregation Induced by Copper(II) and Heparan Sulfate. Pressure-dependent Switch of Reaction Pathways

2008 ◽  
Vol 63 (6) ◽  
pp. 747-755 ◽  
Author(s):  
Driss El Moustaine ◽  
Joan Torrent ◽  
Reinhard Lange
Keyword(s):  
Heparan Sulfate ◽  
Prion Protein ◽  
Conformational Changes ◽  
Atmospheric Pressure ◽  
Amyloid Fibrils ◽  
Copper Ions ◽  
Fibril Formation ◽  
Cellular Prion Protein ◽  
Reaction Pathways ◽  
Structural Alterations

Copper ions (Cu2+) and heparan sulfate (HS) are suspected to act as regulatory agents in the conversion of cellular prion protein (PrPC) to its infectious isoform. However, the mechanism of this reaction is still largely unknown. Our previous report suggested multidimensional pathways for structural alterations of PrP, which may be modulated by high pressure (HP). Here we use HP to investigate the effects of Cu2+ and HS binding on PrP conformational changes and assembly. In the presence of Cu2+, amyloid fibrils are formed only under HP. In contrast, in the presence of HS, fibrils are formed at atmospheric pressure, but not under HP. Both compounds appear to compete for the same binding site, since HS-supported fibril formation is quenched by Cu2+. Inversely, Cu2+- mediated fibril formation under HP is inhibited by HS.

scholarly journals Sulphated glycosaminoglycans prevent the neurotoxicity of a human prion protein fragment

1998 ◽  
Vol 335 (2) ◽  
pp. 369-374 ◽  
Author(s):  
Mar PÉREZ ◽  
Francisco WANDOSELL ◽  
Camilo COLAÇO ◽  
Jesús AVILA
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Transmissible Spongiform Encephalopathies ◽  
Therapeutic Effects ◽  
Protein Fragment ◽  
Spongiform Encephalopathies ◽  
Sulphated Polysaccharides ◽  
Human Prion Protein ◽  
Sulphated Glycosaminoglycans

Although a number of features distinguish the disease isoform of the prion protein (PrPSc) from its normal cellular counterpart (PrPC) in the transmissible spongiform encephalopathies (TSEs), the neuropathogenesis of these diseases remains an enigma. The amyloid fibrils formed by fragments of human PrP have, however, been shown to be directly neurotoxic in vitro. We show here that sulphated polysaccharides (heparin, keratan and chondroitin) inhibit the neurotoxicity of these amyloid fibrils and this appears to be mediated via inhibition of the polymerization of the PrP peptide into fibrils. This provides a rationale for the therapeutic effects of sulphated polysaccharides and suggests a rapid in vitro functional screen for TSE therapeutics.

scholarly journals Parallel β-Sheets and Polar Zippers in Amyloid Fibrils Formed by Residues 10−39 of the Yeast Prion Protein Ure2p

Biochemistry ◽  
2005 ◽  
Vol 44 (31) ◽  
pp. 10669-10680 ◽  
Author(s):  
Jerry C. C. Chan ◽  
Nathan A. Oyler ◽  
Wai-Ming Yau ◽  
Robert Tycko
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Yeast Prion ◽  
Β Sheets

Polymorphism and Ultrastructural Organization of Prion Protein Amyloid Fibrils: An Insight from High Resolution Atomic Force Microscopy

2006 ◽  
Vol 358 (2) ◽  
pp. 580-596 ◽  
Author(s):  
Maighdlin Anderson ◽  
Olga V. Bocharova ◽  
Natallia Makarava ◽  
Leonid Breydo ◽  
Vadim V. Salnikov ◽  
...  
Keyword(s):  
Atomic Force Microscopy ◽  
High Resolution ◽  
Prion Protein ◽  
Amyloid Fibrils ◽  
Ultrastructural Organization ◽  
Force Microscopy ◽  
Atomic Force

scholarly journals Full-length prion protein aggregates to amyloid fibrils and spherical particles by distinct pathways

FEBS Journal ◽  
2008 ◽  
Vol 275 (9) ◽  
pp. 2021-2031 ◽  
Author(s):  
Driss El Moustaine ◽  
Veronique Perrier ◽  
Laszlo Smeller ◽  
Reinhard Lange ◽  
Joan Torrent
Keyword(s):  
Prion Protein ◽  
Amyloid Fibrils ◽  
Protein Aggregates ◽  
Full Length ◽  
Spherical Particles
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