A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform 1 1Edited by M. Yaniv

Peretz, David; Williamson, R. Anthony; Matsunaga, Yoichi; Serban, Hana; Pinilla, Clemencia; Bastidas, Raiza; Rozenshteyn, Roman; James, Thomas Leroy; Houghten, Richard A.; Cohen, Fred E.; Prusiner, Stanley B.; Burton, Dennis R.

doi:10.1006/jmbi.1997.1328

Cited by 325 publications

(307 citation statements)

References 41 publications

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“…Further strands sometimes form in the remaining part that was included in the simulation. Antibody studies indicate that residues 90-120 undergo a conformational change upon conversion to PrP Sc [112][113][114] and a range of studies support the involvement of residues in this region in PrP Sc formation [108,110,111,115]. Our misfolding simulations also indicate the formation of an isolated strand in the loop preceding HA (res.…”

Section: Misfolding and Aggregationsupporting

confidence: 57%

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Kamp

Daggett

2011

Topics in Current Chemistry

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Section: Misfolding and Aggregationsupporting

confidence: 57%

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Kamp

Daggett

2011

Topics in Current Chemistry

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“…The chemical shift changes observed here suggest some change in conformational preferences for this region of the protein, the small C ␣ and CЈ chemical shift changes indicating that it may be sampling more extended conformations, within ␤-PrP. This region becomes partially secluded in PrP Sc (71), and undergoes a conformational change that is essential in prion propagation (72,73).…”

Section: Resultsmentioning

confidence: 75%

Conformational Properties of β-PrP

Hosszu

Trevitt

Jones

et al. 2009

Journal of Biological Chemistry

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Prion propagation involves a conformational transition of the cellular form of prion protein (PrP C ) to a disease-specific isomer (PrP Sc ), shifting from a predominantly ␣-helical conformation to one dominated by ␤-sheet structure. This conformational transition is of critical importance in understanding the molecular basis for prion disease. Here, we elucidate the conformational properties of a disulfide-reduced fragment of human PrP spanning residues 91-231 under acidic conditions, using a combination of heteronuclear NMR, analytical ultracentrifugation, and circular dichroism. We find that this form of the protein, which similarly to PrP Sc , is a potent inhibitor of the 26 S proteasome, assembles into soluble oligomers that have significant ␤-sheet content. The monomeric precursor to these oligomers exhibits many of the characteristics of a molten globule intermediate with some helical character in regions that form helices I and III in the PrP C conformation, whereas helix II exhibits little evidence for adopting a helical conformation, suggesting that this region is a likely source of interaction within the initial phases of the transformation to a ␤-rich conformation. This precursor state is almost as compact as the folded PrP C structure and, as it assembles, only residues 126 -227 are immobilized within the oligomeric structure, leaving the remainder in a mobile, random-coil state.

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“…28,29 Within this region, PrP90-129 appears to be crucial for the conformational changes, 30 whereas PrP90-120 residues are exposed in PrP c but not in PrP sc . 31 In this study, we investigated 10 anti-PrP mAbs against region PrP90-120. While the linear peptide PrP90-120 of human PrP was used as the selection target, all 10 anti-PrP bound intact PrP c on the cell surface.…”

Section: Discussionmentioning

confidence: 99%

Detection of prion epitopes on PrP^c and PrP^sc of transmissible spongiform encephalopathies using specific monoclonal antibodies to PrP

et al. 2005

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Summary Amino acid residues 90-120 of the prion protein (PrP) are likely to be critical for the conversion of PrP c to PrP sc in the transmissible spongiform encephalopathies. We raised 10 monoclonal antibodies against the 90-120 amino acid region, mapped the epitope specificity of these anti-PrP antibodies, and investigated the expression of epitopes recognized by the antibodies in both PrP c and PrP sc . Four out of five of the anti-PrP antibodies raised in a prion knockout mouse immunized with the linear peptide of PrP90-120 could detect PrP sc in 'native' and denatured forms and PrP c in normal cells, as well as recognize epitopes within PrP93-112 residues. In contrast, the other six anti-PrP reagents, including five raised from the two knockout mice immunized with conformationally modified PrP90-120 peptide, could detect PrP c and recognize epitopes within PrP93-107 residues. Four of these reagents could also detect denatured PrP sc on western blots but not PrP sc plaques in brain tissue. The results indicate that residues PrP93-102 are exposed in PrP c but are buried upon conversion to the PrP sc isoform. Furthermore, PrP103-107 residues are partially buried in PrP sc while only the PrP107-112 epitope remains exposed, suggesting that the region PrP93-112 undergoes conformational changes during its conversion to PrP sc .

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A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform 1 1Edited by M. Yaniv

Cited by 325 publications

References 41 publications

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Conformational Properties of β-PrP

Detection of prion epitopes on PrP^c and PrP^sc of transmissible spongiform encephalopathies using specific monoclonal antibodies to PrP

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A conformational transition at the N terminus of the prion protein features in formation of the scrapie isoform 1 1Edited by M. Yaniv

Cited by 325 publications

References 41 publications

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Molecular Dynamics as an Approach to Study Prion Protein Misfolding and the Effect of Pathogenic Mutations

Conformational Properties of β-PrP

Detection of prion epitopes on PrPc and PrPsc of transmissible spongiform encephalopathies using specific monoclonal antibodies to PrP

Contact Info

Product

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About

Detection of prion epitopes on PrP^c and PrP^sc of transmissible spongiform encephalopathies using specific monoclonal antibodies to PrP