Assemblages of prion fragments: novel model systems for understanding amyloid toxicity

Satheeshkumar, K. S.; Jayaraman, Murali; Rajadas, Jayakumar

doi:10.1016/j.jsb.2004.05.006

Cited by 10 publications

(3 citation statements)

References 85 publications

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“…A gradual loss of random coil structure over time, commensurate with the gain in β-sheet structure, was observed during the process of structural transition (Table 1). In the past, we have observed similar structural transitions for other amyloid forming peptides [35,46,47,48,49,50]. Such transitions are well-known in other amyloid aggregates that are associated with protein conformational diseases [51,52,53,54,55].…”

Section: Resultssupporting

confidence: 62%

Solvent Microenvironments and Copper Binding Alters the Conformation and Toxicity of a Prion Fragment

et al. 2013

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The secondary structures of amyloidogenic proteins are largely influenced by various intra and extra cellular microenvironments and metal ions that govern cytotoxicity. The secondary structure of a prion fragment, PrP(111-126), was determined using circular dichroism (CD) spectroscopy in various microenvironments. The conformational preferences of the prion peptide fragment were examined by changing solvent conditions and pH, and by introducing external stress (sonication). These physical and chemical environments simulate various cellular components at the water-membrane interface, namely differing aqueous environments and metal chelating ions. The results show that PrP(111-126) adopts different conformations in assembled and non-assembled forms. Aging studies on the PrP(111-126) peptide fragment in aqueous buffer demonstrated a structural transition from random coil to a stable β-sheet structure. A similar, but significantly accelerated structural transition was observed upon sonication in aqueous environment. With increasing TFE concentrations, the helical content of PrP(111-126) increased persistently during the structural transition process from random coil. In aqueous SDS solution, PrP(111-126) exhibited β-sheet conformation with greater α-helical content. No significant conformational changes were observed under various pH conditions. Addition of Cu2+ ions inhibited the structural transition and fibril formation of the peptide in a cell free in vitro system. The fact that Cu2+ supplementation attenuates the fibrillar assemblies and cytotoxicity of PrP(111-126) was witnessed through structural morphology studies using AFM as well as cytotoxicity using MTT measurements. We observed negligible effects during both physical and chemical stimulation on conformation of the prion fragment in the presence of Cu2+ ions. The toxicity of PrP(111-126) to cultured astrocytes was reduced following the addition of Cu2+ ions, owing to binding affinity of copper towards histidine moiety present in the peptide.

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Section: Resultssupporting

confidence: 62%

Solvent Microenvironments and Copper Binding Alters the Conformation and Toxicity of a Prion Fragment

et al. 2013

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“…67 A recent report has identified two other peptide fragments, hPrP 119-126 and hPrP 121-127 , that can readily form amyloid-like fibrils and can be cytotoxic to astrocytes. 70 These fragments include, at least in part, the region 118-128 of the sequence (Fig. 4a).…”

Section: Human Prion Protein (Hprp)mentioning

confidence: 99%

Prediction of Aggregation-Prone Regions in Structured Proteins

Tartaglia

Pawar

Campioni

et al. 2008

Journal of Molecular Biology

419

485

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“…Numerous peptides derived from the prion protein sequences form amyloid-like fibrils (Jamin et al, 2002;Satheeshkumar and Jayakumar, 2003;Satheeshkumar et al, 2004;Tagliavini et al, 2001). These peptides comprise fragments covering part of or entire secondary structural elements of the prion protein.…”

Section: Introductionmentioning

confidence: 99%

A cylinder-shaped double ribbon structure formed by an amyloid hairpin peptide derived from the β-sheet of murine PrP: An X-ray and molecular dynamics simulation study

Croixmarie

Briki²,

David³

et al. 2005

Journal of Structural Biology

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Assemblages of prion fragments: novel model systems for understanding amyloid toxicity

Cited by 10 publications

References 85 publications

Solvent Microenvironments and Copper Binding Alters the Conformation and Toxicity of a Prion Fragment

Solvent Microenvironments and Copper Binding Alters the Conformation and Toxicity of a Prion Fragment

Prediction of Aggregation-Prone Regions in Structured Proteins

A cylinder-shaped double ribbon structure formed by an amyloid hairpin peptide derived from the β-sheet of murine PrP: An X-ray and molecular dynamics simulation study

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