Abstract
The Alzheimer's β-peptide in neutral aqueous solution is characterized variously as a random coil or a heterogeneous mixture of conformers. Under conditions of lowered pH characteristic of intracellular compartments such as endosomes or lysosomes, a different conformation is favored, which is reflected in the biophysical and biological properties of the peptide. The reactivity of the epitope of the monoclonal antibody 6F/3D, encompassing residues 9-14, is drastically reduced. The fluorescence of human sequence β(1-40) with the tyrosine at position 10 substituted with tryptophan (Y10W β(1-40)) is quenched nearly 50% when the peptide is shifted to pH 4.6. The exposure of the 6F/3D epitope parallels Y10W β(1-40) fluorescence changes induced by a variety of perturbations. The linkage of the sensitivity of immunological detection with the potential for monitoring rapid changes by fluorescence offers convergence of biology and biophysics in the study of β-amyloid peptide conformation.
Original language | English |
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Pages (from-to) | 112-122 |
Number of pages | 11 |
Journal | Archives of Biochemistry and Biophysics |
Volume | 417 |
Issue number | 1 |
DOIs | |
State | Published - Sep 1 2003 |
Bibliographical note
Funding Information:Funding for this work was provided by the Sanders-Brown Center on Aging and the Chandler Medical Center of the University of Kentucky.
Keywords
- 6F/3D
- Antibody
- Conformation
- ELISA
- Epitope
- Fluoroalcohol
- PH
- Trimethylamine-N-oxide
- Tryptophan fluorescence
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology