Copper Binding to the N-Terminal Tandem Repeat Region of Mammalian and Avian Prion Protein: Structural Studies Using Synthetic Peptides

Hornshaw, Martin; McDermott, J.R.; Candy, Judith M.; Lakey, Jeremy H.

doi:10.1006/bbrc.1995.2384

Cited by 299 publications

(274 citation statements)

References 0 publications

Supporting

Mentioning

260

Contrasting

Unclassified

Order By: Relevance

“…34 In addition, short peptides corresponding to the octapeptide repeat motif of PrP have been reported to bind Cu2ϩ. 35,36 Moreover, it has been shown that PrP fragments can be transformed from a predominantly ␣-helical monomeric form to an oligomeric ␤-sheet-rich secondary structure. 37,38 Therefore, PrP sc fragments with a distinct structure could have different neurotoxic properties or a tendency to form aggregates, providing a possible mechanism underlying the differences in phenotypic presentation among GSS variants.…”

Section: Discussionmentioning

confidence: 99%

Prion Proteins with Different Conformations Accumulate in Gerstmann-Sträussler-Scheinker Disease Caused by A117V and F198S Mutations

Piccardo

Liepnieks

William

et al. 2001

The American Journal of Pathology

View full text Add to dashboard Cite

Gerstmann-Sträussler-Scheinker disease (GSS) ischaracterized by the accumulation of proteinase K (PK)-resistant prion protein fragments (PrP sc ) of ϳ7 to 15 kd in the brain. Purified GSS amyloid is composed primarily of ϳ7-kd PrP peptides, whose N terminus corresponds to residues W 81 and G 88 to G 90 in patients with the A117V mutation and to residue W 81 in patients with the F198S mutation. The aim of this study was to characterize PrP in brain extracts, microsomal preparations, and purified fractions from A117V patients and to determine the N terminus of PrP sc species in both GSS A117V and F198S. In all GSS A117V patients, the ϳ7-kd PrP sc fragment isolated from nondigested and PK-digested samples had the major N terminus at residue G 88 and G 90 , respectively. Conversely, in all patients with GSS F198S, an ϳ8-kd Prion diseases are neurodegenerative disorders present in both humans and animals.

show abstract

Section: Discussionmentioning

confidence: 99%

Prion Proteins with Different Conformations Accumulate in Gerstmann-Sträussler-Scheinker Disease Caused by A117V and F198S Mutations

Piccardo

Liepnieks

William

et al. 2001

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…By using synthetic peptides, several authors have reported that the OR region of PrP c binds Cu 2+ , and to a lesser extent Cu + , thereby modulating its intracellular levels (e.g., (Hornshaw et al, 1995a;Hornshaw et al, 1995b)). Indeed, synaptosomal fractions have revealed that the amount of copper in the brain of PrP c knockout mice is lower than in wild-type (WT) counterparts (Herms et al, 1999).…”

Section: Prp C Andmentioning

confidence: 99%

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

Nicolas

Gavı́n

Rı́o

2009

Brain Research Reviews

View full text Add to dashboard Cite

show abstract

“…A recent mass spectrometric study has shown that the octapeptide repeat provides a binding site for divalent metal ions, preferentially for Cu(II) [15]. The structure of a peptide consisting of four tandem repeats of the octapeptide has been investigated in the presence and absence of Cu(II) by using circular dichroism (CD) spectroscopy [16]. Although the CD spectrum was affected by the metal binding, the peptide secondary structure could not be fully revealed due to a strong distortion of the spectrum by the tryptophan residues.…”

Section: Introductionmentioning

confidence: 99%

Metal‐dependent α‐helix formation promoted by the glycine‐rich octapeptide region of prion protein

1996

View full text Add to dashboard Cite

Prion diseases share a common feature in that the normal cellular prion .protein (PrP c) converts to a proteaseresistant isoform PrP ~c. The c¢-helix-rich C-terminal half of PrP c is partly converted into []-sheet in PrP so. We have examined by Raman spectroscopy the structure of an octapeptide PHGGGWGQ that appears in the N-terminal region of PrP c and a longer peptide containing the octapeptide region. The peptides do not assume any regular structure without divalent metal ions, whereas Cu(II) binding to the HGGG segment induces formation of co-helical structure on the C-terminal side of the peptide chain. The N-terminal octapeptide of prion protein may be a novel structural motif that acts as a promoter of c~-helix formation.

show abstract

Copper Binding to the N-Terminal Tandem Repeat Region of Mammalian and Avian Prion Protein: Structural Studies Using Synthetic Peptides

Cited by 299 publications

References 0 publications

Prion Proteins with Different Conformations Accumulate in Gerstmann-Sträussler-Scheinker Disease Caused by A117V and F198S Mutations

Prion Proteins with Different Conformations Accumulate in Gerstmann-Sträussler-Scheinker Disease Caused by A117V and F198S Mutations

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

Metal‐dependent α‐helix formation promoted by the glycine‐rich octapeptide region of prion protein

Contact Info

Product

Resources

About