The 118–135 peptide of the human prion protein forms amyloid fibrils and induces liposome fusion

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.

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Molecular Structure of Amyloid Fibrils Formed by Residues 127 to 147 of the Human Prion Protein

Chemistry - A European Journal ◽

10.1002/chem.200903290 ◽

2010 ◽

Vol 16 (18) ◽

pp. 5492-5499 ◽

Cited By ~ 18

Author(s):

Ni-Shian Lin ◽

John Ching-Hao Chao ◽

Hsin-Mei Cheng ◽

Fang-Chieh Chou ◽

Chi-Fon Chang ◽

...

Keyword(s):

Molecular Structure ◽

Prion Protein ◽

Amyloid Fibrils ◽

Human Prion Protein

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Native, amyloid fibrils and β-oligomers of the C-terminal domain of human prion protein display differential activation of complement and bind C1q, factor H and C4b-binding protein directly

Molecular Immunology ◽

10.1016/j.molimm.2008.02.023 ◽

2008 ◽

Vol 45 (11) ◽

pp. 3213-3221 ◽

Cited By ~ 23

Author(s):

Andreas P. Sjöberg ◽

Sofie Nyström ◽

Per Hammarström ◽

Anna M. Blom

Keyword(s):

Prion Protein ◽

Amyloid Fibrils ◽

Binding Protein ◽

Factor H ◽

Differential Activation ◽

Terminal Domain ◽

Human Prion Protein

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

10.1101/2021.08.10.455830 ◽

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.

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Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation

Journal of General Virology ◽

10.1099/vir.0.81630-0 ◽

2006 ◽

Vol 87 (8) ◽

pp. 2443-2449 ◽

Cited By ~ 23

Author(s):

Patrick A. Lewis ◽

M. Howard Tattum ◽

Samantha Jones ◽

Daljit Bhelt ◽

Mark Batchelor ◽

...

Keyword(s):

Prion Protein ◽

Amyloid Fibrils ◽

Prion Diseases ◽

Amyloid Formation ◽

Native Structure ◽

Prion Strain ◽

Profound Influence ◽

Human Prion Protein ◽

Kinetics Of ◽

Codon 129

The human prion protein (PrP) has a common polymorphism at residue 129, which can be valine or methionine. This polymorphism has a strong influence on susceptibility to prion diseases and on prion-strain properties. Previous work has shown that this amino acid variation has no measurable effect on the native structure of cellular PrP (PrPC). Here, it is shown that the polymorphism does not change the efficiency of conversion to the β-PrP conformation or affect the binding of copper(II) ions. However, in a partially denatured conformation, the polymorphic variation has a profound influence on the ability of the protein to form amyloid fibrils spontaneously.

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