Home > Research > Publications & Outputs > Aggregation and metal-binding properties of mut...

Research

Links

Text available via DOI:

Keywords

View graph of relations

Aggregation and metal-binding properties of mutant forms of the amyloid Aβ peptide of Alzheimer's disease

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Published

Standard

Aggregation and metal-binding properties of mutant forms of the amyloid Aβ peptide of Alzheimer's disease. / Clements, A; Allsop, D; Walsh, D M et al.
In: Journal of Neurochemistry, Vol. 66, No. 2, 02.1996, p. 740-747.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Clements, A, Allsop, D, Walsh, DM & Williams, CH 1996, 'Aggregation and metal-binding properties of mutant forms of the amyloid Aβ peptide of Alzheimer's disease', Journal of Neurochemistry, vol. 66, no. 2, pp. 740-747. https://doi.org/10.1046/j.1471-4159.1996.66020740.x

APA

Clements, A., Allsop, D., Walsh, D. M., & Williams, C. H. (1996). Aggregation and metal-binding properties of mutant forms of the amyloid Aβ peptide of Alzheimer's disease. Journal of Neurochemistry, 66(2), 740-747. https://doi.org/10.1046/j.1471-4159.1996.66020740.x

Vancouver

Clements A, Allsop D, Walsh DM, Williams CH. Aggregation and metal-binding properties of mutant forms of the amyloid Aβ peptide of Alzheimer's disease. Journal of Neurochemistry. 1996 Feb;66(2):740-747. doi: 10.1046/j.1471-4159.1996.66020740.x

Author

Clements, A ; Allsop, D ; Walsh, D M et al. / Aggregation and metal-binding properties of mutant forms of the amyloid Aβ peptide of Alzheimer's disease. In: Journal of Neurochemistry. 1996 ; Vol. 66, No. 2. pp. 740-747.

Bibtex

@article{9b47831ffb2b445bb12ee7e9eb93d302,
title = "Aggregation and metal-binding properties of mutant forms of the amyloid Aβ peptide of Alzheimer's disease",
abstract = "The fibrillogenic properties of Alzheimer's A beta peptides corresponding to residues 1-40 of the normal human sequence and to two mutant forms containing the replacement Ala21 to Gly or Glu22 to Gln were compared. At pH 7.4 and 37 degrees C the Gln22 peptide was found to aggregate and precipitate from solution faster than the normal A beta, whereas the Gly21 peptide aggregated much more slowly. Electron microscopy showed that the aggregates all had fibrillar structures. Circular dichroism spectra of these peptides revealed that aggregation of the normal and Gln22 sequences was associated with spectral changes consistent with a transformation from random coil to beta sheet, whereas the spectrum of the Gly21 peptide remained almost unchanged during a period in which little or no aggregation occurred. When immobilised by spotting onto nitrocellulose membranes the peptides bound similar amounts of the radioisotope 65Zn2+. Of several competing metal ions, tested at 20x the concentration of Zn2+, Cu2+ displaced > 95% of the radioactivity from all three peptides and Ni2+ produced >50% displacement in each case. Some other metal ions tested caused lesser displacement, but Fe2+ and Al3+ were without effect. In a saturation binding assay, a value of 3.2 microM was obtained for the binding of Zn2+ to A beta but our data provided no evidence for a reported higher affinity site (107 nM). The results suggest that the neuropathology associated with the Gly21 mutation is not due to enhanced fibrillogenic or different metal-binding properties of the peptide and that the binding of zinc to amyloid peptides is not a specific phenomenon.",
keywords = "Alzheimer Disease, Amino Acid Sequence, Amyloid beta-Peptides, Circular Dichroism, Humans, Metals, Microscopy, Electron, Molecular Sequence Data, Mutation, Peptide Fragments",
author = "A Clements and D Allsop and Walsh, {D M} and Williams, {C H}",
year = "1996",
month = feb,
doi = "10.1046/j.1471-4159.1996.66020740.x",
language = "English",
volume = "66",
pages = "740--747",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

RIS

TY - JOUR

T1 - Aggregation and metal-binding properties of mutant forms of the amyloid Aβ peptide of Alzheimer's disease

AU - Clements, A

AU - Allsop, D

AU - Walsh, D M

AU - Williams, C H

PY - 1996/2

Y1 - 1996/2

N2 - The fibrillogenic properties of Alzheimer's A beta peptides corresponding to residues 1-40 of the normal human sequence and to two mutant forms containing the replacement Ala21 to Gly or Glu22 to Gln were compared. At pH 7.4 and 37 degrees C the Gln22 peptide was found to aggregate and precipitate from solution faster than the normal A beta, whereas the Gly21 peptide aggregated much more slowly. Electron microscopy showed that the aggregates all had fibrillar structures. Circular dichroism spectra of these peptides revealed that aggregation of the normal and Gln22 sequences was associated with spectral changes consistent with a transformation from random coil to beta sheet, whereas the spectrum of the Gly21 peptide remained almost unchanged during a period in which little or no aggregation occurred. When immobilised by spotting onto nitrocellulose membranes the peptides bound similar amounts of the radioisotope 65Zn2+. Of several competing metal ions, tested at 20x the concentration of Zn2+, Cu2+ displaced > 95% of the radioactivity from all three peptides and Ni2+ produced >50% displacement in each case. Some other metal ions tested caused lesser displacement, but Fe2+ and Al3+ were without effect. In a saturation binding assay, a value of 3.2 microM was obtained for the binding of Zn2+ to A beta but our data provided no evidence for a reported higher affinity site (107 nM). The results suggest that the neuropathology associated with the Gly21 mutation is not due to enhanced fibrillogenic or different metal-binding properties of the peptide and that the binding of zinc to amyloid peptides is not a specific phenomenon.

AB - The fibrillogenic properties of Alzheimer's A beta peptides corresponding to residues 1-40 of the normal human sequence and to two mutant forms containing the replacement Ala21 to Gly or Glu22 to Gln were compared. At pH 7.4 and 37 degrees C the Gln22 peptide was found to aggregate and precipitate from solution faster than the normal A beta, whereas the Gly21 peptide aggregated much more slowly. Electron microscopy showed that the aggregates all had fibrillar structures. Circular dichroism spectra of these peptides revealed that aggregation of the normal and Gln22 sequences was associated with spectral changes consistent with a transformation from random coil to beta sheet, whereas the spectrum of the Gly21 peptide remained almost unchanged during a period in which little or no aggregation occurred. When immobilised by spotting onto nitrocellulose membranes the peptides bound similar amounts of the radioisotope 65Zn2+. Of several competing metal ions, tested at 20x the concentration of Zn2+, Cu2+ displaced > 95% of the radioactivity from all three peptides and Ni2+ produced >50% displacement in each case. Some other metal ions tested caused lesser displacement, but Fe2+ and Al3+ were without effect. In a saturation binding assay, a value of 3.2 microM was obtained for the binding of Zn2+ to A beta but our data provided no evidence for a reported higher affinity site (107 nM). The results suggest that the neuropathology associated with the Gly21 mutation is not due to enhanced fibrillogenic or different metal-binding properties of the peptide and that the binding of zinc to amyloid peptides is not a specific phenomenon.

KW - Alzheimer Disease

KW - Amino Acid Sequence

KW - Amyloid beta-Peptides

KW - Circular Dichroism

KW - Humans

KW - Metals

KW - Microscopy, Electron

KW - Molecular Sequence Data

KW - Mutation

KW - Peptide Fragments

U2 - 10.1046/j.1471-4159.1996.66020740.x

DO - 10.1046/j.1471-4159.1996.66020740.x

M3 - Journal article

C2 - 8592147

VL - 66

SP - 740

EP - 747

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -