Y10W β(1–40) fluorescence reflects epitope exposure in conformers of Alzheimer’s β-peptide

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.