Parallel In-register Intermolecular β-Sheet Architectures for Prion-seeded Prion Protein (PrP) Amyloids

Groveman, Bradley R.; Dolan, Michael; Taubner, Lara M.; Kraus, Allison; Wickner, Reed B.; Caughey, Byron

doi:10.1074/jbc.m114.578344

Cited by 156 publications

(220 citation statements)

References 68 publications

Supporting

Mentioning

208

Contrasting

Order By: Relevance

“…14 In light of severely broadened lines in spectra of uniformly 13 C, 15 N-labeled fibrils, however, only residue types could be partially assigned to cross peak clusters. Assignment probabilities predicted by a Monte Carlo/simulated annealing algorithm suggested a fibril core comprising the 173-224 segment but could not rule out an involvement of the 95-161 segment.…”

Section: Introductionmentioning

confidence: 99%

“…15 Taken together, there is a need for improved protocols and additional experimental data to discriminate among different models for amyloid fibrils of PrP and to understand which structural features can render proteins infectious. The lack of high-resolution data is not only due to the general challenge posed to structure analysis by insoluble, non-crystalline, and heterogeneous samples, but also to the impossibility to prepare NMR-sufficient amounts of homogeneous brain-purified samples.…”

Section: Introductionmentioning

confidence: 99%

“…[16][17][18] Consequently, seeded fibril growth can be exploited to amplify and label structures present in brain tissue. 15,19,20 Likewise, different strains of the yeast prion Sup35p were faithfully passed on to recombinantly expressed Sup35p monomers by seeding with yeast cell lysates. 21 In contrast to all other amyloid fibrils, in vitro-generated PrPamyloid offers the crucial advantage that its physiological relevance to neurodegenerative diseases in mammals can be assessed directly.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Progress towards structural understanding of infectious sheep PrP-amyloid

Müller

Brener

Andréoletti

et al. 2014

Prion

View full text Add to dashboard Cite

The still elusive structural difference of non-infectious and infectious amyloid of the mammalian prion protein (PrP) is a major pending milestone in understanding protein-mediated infectivity in neurodegenerative diseases. Preparations of PrP-amyloid proven to be infectious have never been investigated with a high-resolution technique. All available models to date have been based on low-resolution data. Here, we establish protocols for the preparation of infectious samples of full-length recombinant (rec) PrP-amyloid in NMR-sufficient amounts by spontaneous fibrillation and seeded fibril growth from brain extract. We link biological and structural data of infectious recPrP-amyloid, derived from bioassays, atomic force microscopy, and solid-state NMR spectroscopy. Our data indicate a semi-mobile N-terminus, some residues with secondary chemical shifts typical of a-helical secondary structure in the middle part between »115 to »155, and a distinct b-sheet core C-terminal of residue »155. These findings are not in agreement with all current models for PrP-amyloid. We also provide evidence that samples seeded from brain extract may not differ in the overall arrangement of secondary structure elements, but rather in the flexibility of protein segments outside the b-core region. Taken together, our protocols provide an essential basis for the high-resolution characterization of non-infectious and infectious PrP-amyloid in the near future.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Progress towards structural understanding of infectious sheep PrP-amyloid

Müller

Brener

Andréoletti

et al. 2014

Prion

View full text Add to dashboard Cite

show abstract

“…1 Both conformers displayed a high degree of protection against solvent exchange, consistent with previous DXMS studies of mammalian prions and with those PrP Sc models that propose a complete refolding of the PrP C-terminus to b-sheet secondary structure. 1,[4][5][6][7][8] Despite the striking structural similarities between the infectious and non-infectious PrP conformers, structural differences were detected in 2 restricted C-terminal domains, including residues 91-115 and 144-163 (mouse PrP numbering). 1 Within these domains, the non-infectious conformer appears to have relatively increased solvent accessibility.…”

Section: Infectious and Non-infectious Recombinant Prp Conformers Difmentioning

confidence: 99%

Dissociation of recombinant prion autocatalysis from infectivity

Noble¹,

Supattapone

2015

Prion

View full text Add to dashboard Cite

“…[34][35][36] One of the main challenges is to obtain homogeneous material from infected brain in sufficient amount for the structural studies. Besides, there are also safety limitations for the study of bona fide infectious mammalian prions.…”

Section: Applications Of Bacterially Generated Mammalian Prion Amyloidsmentioning

confidence: 99%

Mammalian prion amyloid formation in bacteria

Macedo

Cordeiro

Ventura

2016

Prion

View full text Add to dashboard Cite

ABSTRACT. Mammalian prion proteins (PrPs) that cause transmissible spongiform encephalopathies are misfolded conformations of the host cellular PrP. The misfolded form, the scrapie PrP (PrP Sc ), can aggregate into amyloid fibrils that progressively accumulate in the brain, evolving to a pathological phenotype. A particular characteristic of PrP Sc is to be found as different strains, related to the diversity of conformational states it can adopt. Prion strains are responsible for the multiple phenotypes observed in prion diseases, presenting different incubation times and diverse deposition profiles in the brain. PrP biochemical properties are also strain-dependent, such as different digestion pattern after proteolysis and different stability. Although they have long been studied, strain formation is still a major unsolved issue in prion biology. The recreation of strainspecific conformational features is of fundamental importance to study this unique pathogenic phenomenon. In our recent paper, we described that murine PrP, when expressed in bacteria, forms amyloid inclusion bodies that possess different strain-like characteristics, depending on the PrP construct. Here, we present an extra-view of these data and propose that bacteria might become a successful model to generate preparative amounts of prion strain-specific assemblies for highresolution structural analysis as well as for addressing the determinants of infectivity and transmissibility.

show abstract

Parallel In-register Intermolecular β-Sheet Architectures for Prion-seeded Prion Protein (PrP) Amyloids

Cited by 156 publications

References 68 publications

Progress towards structural understanding of infectious sheep PrP-amyloid

Progress towards structural understanding of infectious sheep PrP-amyloid

Dissociation of recombinant prion autocatalysis from infectivity

Mammalian prion amyloid formation in bacteria

Contact Info

Product

Resources

About