scholarly journals Strain-dependent profile of misfolded prion protein aggregates

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Rodrigo Morales ◽  
Ping Ping Hu ◽  
Claudia Duran-Aniotz ◽  
Fabio Moda ◽  
Rodrigo Diaz-Espinoza ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Aggregates ◽  
Strain Dependent

scholarly journals The Physical Relationship between Infectivity and Prion Protein Aggregates Is Strain-Dependent

2010 ◽  
Vol 6 (4) ◽  
pp. e1000859 ◽  
Author(s):  
Philippe Tixador ◽  
Laëtitia Herzog ◽  
Fabienne Reine ◽  
Emilie Jaumain ◽  
Jérôme Chapuis ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Aggregates ◽  
Physical Relationship ◽  
Strain Dependent ◽  
Is Strain

scholarly journals PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Allison Kraus ◽  
Gregory J. Raymond ◽  
Brent Race ◽  
Katrina J. Campbell ◽  
Andrew G. Hughson ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Clinical Signs ◽  
Protein Aggregates ◽  
Structural Features ◽  
Spongiform Encephalopathy ◽  
Specific Sequence

ABSTRACT Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro, only some are transmissible and pathogenic in vivo. To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro. Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood. Here we have compared the combined effects of prion seeding and mutations of prion protein (PrP) on the structure and transmission properties of synthetic PrP aggregates. Our results highlight the influence of specific sequence features in the normally unstructured region of PrP that influence the infectious and neuropathogenic properties of PrP-derived aggregates.

scholarly journals Immunopurification of Pathological Prion Protein Aggregates

PLoS ONE ◽  
2009 ◽  
Vol 4 (11) ◽  
pp. e7816 ◽  
Author(s):  
Emiliano Biasini ◽  
Laura Tapella ◽  
Susanna Mantovani ◽  
Matteo Stravalaci ◽  
Marco Gobbi ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Aggregates

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

Development of oligomeric prion-protein aggregates in a mouse model of prion disease

2009 ◽  
Vol 219 (1) ◽  
pp. 123-130 ◽  
Author(s):  
Kensuke Sasaki ◽  
Haruhiko Minaki ◽  
Toru Iwaki
Keyword(s):  
Mouse Model ◽  
Prion Protein ◽  
Prion Disease ◽  
Protein Aggregates

scholarly journals Paradoxical Role of Prion Protein Aggregates in Redox-Iron Induced Toxicity

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11420 ◽  
Author(s):  
Dola Das ◽  
Xiu Luo ◽  
Ajay Singh ◽  
Yaping Gu ◽  
Soumya Ghosh ◽  
...  
Keyword(s):  
Prion Protein ◽  
Protein Aggregates

scholarly journals Cryo-EM structure of disease-related prion fibrils provides insights into seeding barriers

2021 ◽  
Author(s):  
Qiuye Li ◽  
Christopher P. Jaroniec ◽  
Witold K. Surewicz
Keyword(s):  
High Resolution ◽  
Prion Protein ◽  
Prion Disease ◽  
Amyloid Fibrils ◽  
Prion Diseases ◽  
Protein Aggregates ◽  
Direct Support ◽  
Human Prion Protein ◽  
Structural Insight

One of the least understood aspects of prion diseases is the structure of infectious prion protein aggregates. Here we report a high-resolution cryo-EM structure of amyloid fibrils formed by human prion protein with Y145Stop mutation that is associated with a familial prion disease. This structural insight allows us not only to explain previous biochemical findings, but also provides direct support for the conformational adaptability model of prion transmissibility barriers.

scholarly journals A bacteria-based genetic assay detects prion formation

2019 ◽  
Vol 116 (10) ◽  
pp. 4605-4610 ◽  
Author(s):  
Eleanor Fleming ◽  
Andy H. Yuan ◽  
Danielle M. Heller ◽  
Ann Hochschild
Keyword(s):  
Dna Binding ◽  
Neurodegenerative Diseases ◽  
Prion Protein ◽  
Protein Aggregates ◽  
Dna Binding Protein ◽  
Bacterial Cells ◽  
Yeast Prion ◽  
Genetic Tool ◽  
Domains Of Life ◽  
Genetic Assay

Prions are infectious, self-propagating protein aggregates that are notorious for causing devastating neurodegenerative diseases in mammals. Recent evidence supports the existence of prions in bacteria. However, the evaluation of candidate bacterial prion-forming proteins has been hampered by the lack of genetic assays for detecting their conversion to an aggregated prion conformation. Here we describe a bacteria-based genetic assay that distinguishes cells carrying a model yeast prion protein in its nonprion and prion forms. We then use this assay to investigate the prion-forming potential of single-stranded DNA-binding protein (SSB) ofCampylobacter hominis. Our findings indicate that SSB possesses a prion-forming domain that can transition between nonprion and prion conformations. Furthermore, we show that bacterial cells can propagate the prion form over 100 generations in a manner that depends on the disaggregase ClpB. The bacteria-based genetic tool we present may facilitate the investigation of prion-like phenomena in all domains of life.

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