Y10W beta(1-40) fluorescence reflects epitope exposure in conformers of Alzheimer's beta-peptide.
The Alzheimer's beta-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 beta(1-40) with the tyrosine at position 10 substituted with tryptophan (Y10W beta(1-40)) is quenched nearly 50% when the peptide is shifted to pH 4.6. The exposure of the 6F/3D epitope parallels Y10W beta(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 beta-amyloid peptide conformation.
LeVine
Harry
H
Department of Molecular and Cellular Biochemistry, Chandler School of Medicine, University of Kentucky, 209 Sanders-Brown Building, 800 S. Limestone Street, Lexington, KY 40536-0230, USA. hlevine@email.uky.edu
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000939:Epitopes / Q000187:drug effects*; D005453:Fluorescence; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008744:Methylamines / Q000494:pharmacology; D008969:Molecular Sequence Data; D016877:Oxidants / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry* / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020005:Propanols / Q000494:pharmacology; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012996:Solutions; D012997:Solvents; D013997:Time Factors; D014364:Tryptophan / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000939:Epitopes; D008744:Methylamines; D016877:Oxidants; D010446:Peptide Fragments; D020005:Propanols; D011994:Recombinant Proteins; D012996:Solutions; D012997:Solvents; D014364:Tryptophan; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated; C005855:trimethyloxamine