Prions articles within Nature Communications

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  • Article
    | Open Access

    Alzheimer’s plaques contain a high amount of Aβ fibrils and a high concentration of lipids. The authors determined structures of Aβ40 fibrils grown in the presence of lipids, revealing high-resolution details of potentially disease-relevant fibril-lipid interactions.

    • Benedikt Frieg
    • , Mookyoung Han
    •  & Gunnar F. Schröder

  • Article
    | Open Access

    Cells form non-pathological amyloids to survive stressful conditions. Marijan et al. show that heat shock-induced aggregation is self-regulated by protein stability, with high-ordered motifs acting as thermo-switches that control amyloidogenesis.

    • Dane Marijan
    • , Evgenia A. Momchilova
    •  & Timothy E. Audas

  • Article
    | Open Access

    In this work, the authors report the Cryo-EM structure of PNF-18, a biotechnologically engineered peptide fibril that enhances retroviral infectivity. The peptide fibrils mature into polymorphic amyloid structures in a time-dependent manner. The structure provides insights into the molecular basis of peptide nanofibrils as retroviral transduction enhancers.

    • Thomas Heerde
    • , Desiree Schütz
    •  & Marcus Fändrich

  • Article
    | Open Access

    The authors developed a computational approach to probe the stability of amyloid fibrils and discover networks of hotspot interactions. Understanding the mechanisms of amyloid folding will help identify novel methods to treat protein (mis)folding diseases.

    • Vishruth Mullapudi
    • , Jaime Vaquer-Alicea
    •  & Lukasz A. Joachimiak

  • Article
    | Open Access

    Here the authors describe mechanisms through which analogous LGMDD1 (Limb-Girdle Muscular Dystrophy Type D1) mutations affect Sis1 (a yeast functional homolog of human DNAJB6) chaperone activity and poison the function of wild-type protein; potentially uncovering a new therapeutic route to explore.

    • Ankan K. Bhadra
    • , Michael J. Rau
    •  & Heather L. True

  • Comment
    | Open Access

    The prion hypothesis embodies the radical concept that prion proteins contain the necessary information for infectious replication within their shape, thus obviating the requirement for genomic material. Two elegant papers by Hoyt et al. and Manka et al. describing high-resolution structures of infectious prions bring us closer to answering the long-standing question of how different prion conformations produce heritably distinct diseases.

    • Glenn C. Telling

  • Article
    | Open Access

    High-resolution structures of mammalian prions have remained elusive. Here, Manka et al. report the cryo-EM structure of infectious RML prion fibrils from mice. Structural similarity with recently reported infectious 263K prion fibrils from hamsters now suggests a common prion architecture.

    • Szymon W. Manka
    • , Wenjuan Zhang
    •  & Jonathan D. F. Wadsworth

  • Article
    | Open Access

    Here, the authors present the cryo-EM structure of in vitro amyloid fibrils from recombinant SAA1.1 protein that were formed by seeding with fibrils purified from systemic AA amyloidosis tissue. This in vitro fibril structure resembles the structure of the ex vivo fibrils but differs from unseeded in vitro fibrils. These findings show that fibril morphologies can be propagated in vitro by seeding.

    • Thomas Heerde
    • , Matthies Rennegarbe
    •  & Marcus Fändrich

  • Article
    | Open Access

    Rift Valley fever virus (RVFV) can cause severe diseases in humans, including encephalitis. Here the authors show that NSs, the major virulence factor of RVFV, is an amyloidogenic protein forming fibrils in infected mouse brains and causing increased mortality in mice.

    • Psylvia Léger
    • , Eliana Nachman
    •  & Pierre-Yves Lozach

  • Article
    | Open Access

    Single-molecule in vitro assays require dedicated confocal microscopes equipped with fluorescence correlation spectroscopy (FCS) modules. Here the authors present a compact, cheap and open-source 3D-printed confocal microscope for single photon counting and FCS measurements, and use it to detect α-synuclein aggregation.

    • James W. P. Brown
    • , Arnaud Bauer
    •  & Yann Gambin

  • Article
    | Open Access

    Systemic amyloidosis of the ATTR is one of the most abundant forms of systemic amyloidosis and caused by misfolding of the circulating blood protein transthyretin (TTR). Here the authors present the cryo-EM structure of patient-derived Val30Met ATTR amyloid fibrils which reveals that the protofilament consists of an N-terminal and a C-terminal TTR fragment and discuss implications for the mechanism of misfolding.

    • Matthias Schmidt
    • , Sebastian Wiese
    •  & Marcus Fändrich

  • Article
    | Open Access

    Aβ plaques have been detected in brains of patients with prion diseases. Here, using mice, the authors show that prion infection enhances Aβ production via a PDK1-TACE mechanism and that brain deposition of Aβ induced by Aβ seeds co-transmitted with PrPSc contributes to mortality in prion disease.

    • Juliette Ezpeleta
    • , Vincent Baudouin
    •  & Benoit Schneider

  • Article
    | Open Access

    The biophysical mechanisms of how disease-associated tau mutations drive amyloid formation are not well understood. Here the authors use biophysical approaches, cell models and MD simulations and find that the intrinsically disordered repeat domain of tau encodes a metastable local structure and perturbations through mutations and proline isomerization cause an aggregation phenotype in vitro and in cells.

    • Dailu Chen
    • , Kenneth W. Drombosky
    •  & Lukasz A. Joachimiak

  • Article
    | Open Access

    Prion-forming proteins have been found in animals, plants, fungi, and bacteria. Here, Nan et al. report that a baculovirus-encoded protein behaves as prion in a yeast system and forms aggregates at high multiplicity of infection in insect cells that affect baculovirus replication.

    • Hao Nan
    • , Hongying Chen
    •  & Xiaodong Xu

  • Article
    | Open Access

    Synthetic prions have previously been generated from recombinant rodent PrP. Here the authors generate synthetic human prions, by seeding human PrP with CJD prions, and characterize its infectivity in mice.

    • Chae Kim
    • , Xiangzhu Xiao
    •  & Jiri G. Safar

  • Article
    | Open Access

    It is hypothesised that exposure to bovine spongiform encephalopathy through contaminated food could have resulted in a large proportion of latent variant Creutzfeldt-Jakob disease cases in humans. Here the authors demonstrate that inoculation with blood from non-symptomatic, vCJD infected humans, results in a unique prion-like disorder in mice and macaques.

    • Emmanuel E. Comoy
    • , Jacqueline Mikol
    •  & Jean-Philippe Deslys

  • Article
    | Open Access

    Prion diseases can be transmitted across species. Here the authors use solid-state NMR to study prion protein (PrP) amyloids from human, mouse and Syrian hamster and show that their structural differences are mainly governed by two residues, which helps to understand interspecies PrP propagation on a molecular level.

    • Theint Theint
    • , Philippe S. Nadaud
    •  & Christopher P. Jaroniec

  • Article
    | Open Access

    PrPC protein plays a key role in prion transmission across species. Here, the authors compare transmission of a representative scrapie isolate to transgenic mice expressing variable levels of the same Prnp allele as the donor sheep, and find divergent strain propagation regulated by PrPCgene dosage.

    • Annick Le Dur
    • , Thanh Lan Laï
    •  & Hubert Laude

  • Article |

    Scrapie, a form of prion disease that affects sheep and goats, is believed not to be transmissible to humans. Using transgenic mice expressing human prion protein as a model of cross-species prion transmission, the authors show that ovine scrapie may possess potential to be passed on to humans.

    • Hervé Cassard
    • , Juan-Maria Torres
    •  & Olivier Andréoletti

  • Article |

    The yeast prion Sup35/[PSI+] confers a translation termination defect in its amyloid form. Pezza et al.reveal that aggregated Sup35 retains translation termination activity, and find that fluctuations in the size and composition of aggregates play an important role in determining their activity and toxicity.

    • John A. Pezza
    • , Janice Villali
    •  & Tricia R. Serio

  • Article |

    While N-terminal acetylation has been shown to regulate the function or stability of a limited number of specific proteins, Holmes et al.report that global loss of this modification results in widespread protein misfolding, and show that the resulting stress response contributes to the suppression of a yeast prion phenotype.

    • William M. Holmes
    • , Brian K. Mannakee
    •  & Tricia R. Serio

  • Article
    | Open Access

    Prions (PrP) are infectious agents that cause lethal neurodegenerative diseases. Here the authors study the kinetics of prion propagation in mice and show that the onset of neuropathology occurs during the late phase of disease and is hypothesized to be due to increases in a toxic isoform of PrP that is different from the infectious species.

    • Malin K. Sandberg
    • , Huda Al-Doujaily
    •  & John Collinge

  • Article
    | Open Access

    In Alzheimer's disease, the soluble amyloid beta peptide is known to modulate synaptic function by forming a complex with prion proteins and metabotropic glutamate receptors. Here, Hu et al.show that amyloid beta signalling via this complex facilitates the induction of long-term depression at synapses.

    • Neng-Wei Hu
    • , Andrew J. Nicoll
    •  & Michael J. Rowan

  • Article
    | Open Access

    Prion protein has been suggested to bind toxic amyloid-ß oligomers. Nicollet al.demonstrate that binding to prion protein and prion protein-dependent synaptotoxicity correlate with the presence of a tubular form of amyloid-ß with a defined triple helical structure.

    • Andrew J. Nicoll
    • , Silvia Panico
    •  & John Collinge

  • Article
    | Open Access

    Prion proteins are implicated in a range of neurodegenerative diseases, which are, in part, due to a disruption of metal homeostasis. Wattet al.use selective antagonists to show that prion proteins mediate zinc uptake by interacting with GluA2-lacking, GluA1-containing AMPA receptors.

    • Nicole T. Watt
    • , David R. Taylor
    •  & Nigel M. Hooper

  • Article
    | Open Access

    The ability of synthetic amyloid β-protein to bind to prion proteins and alter synaptic plasticity has been previously reported. Here the relevance of this binding is investigated in brains of Alzheimer's disease patients and the interaction is shown to be blocked by antibodies to two distinct regions of prion proteins.

    • Darragh B. Freir
    • , Andrew J. Nicoll
    •  & John Collinge

  • Article
    | Open Access

    The study of prion diseases has been hampered as there is no method to distinguish newly formed abnormal prion protein conformers. Here, the authors describe a method to study newly formed abnormal prion protein and demonstrate that it is produced within 1 minute of cell exposure to prions.

    • R. Goold
    • , S. Rabbanian
    •  & S.J. Tabrizi

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