A serine-->proline change in the Alzheimer's disease-associated epitope Tau 2 results in altered secondary structure, but phosphorylation overcomes the conformational gap.
Monoclonal antibody Tau 2 was raised against bovine tau protein, was reported to recognize a conformational epitope, and stained tau was found in neurofibrillary tangles of Alzheimer's disease, but not normal human tau. We synthesized tetradeka peptides corresponding to the original bovine sequence, its serine-->proline substituted analog, the genuine human sequence of this region, and the bovine epitope phosphorylated on the crucial serine. The secondary structure of the peptides was determined by circular dichroism. It was found that only the original bovine epitope showed a tendency to form the beta-pleated sheets characteristic of the neurofibrillary tangles. The spectra of the human peptide, its analog, and the phosphorylated bovine sequence were very similar, featuring a weak, helical beta-turn character. Eventual phosphorylation of epitopes of this otherwise heavily phosphorylated protein may overcome inter-species conformational gaps.
Lang
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E
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Otvos
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L
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002417:Cattle; D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010766:Phosphorylation; D011392:Proline; D011487:Protein Conformation; D012694:Serine; D016875:tau Proteins / Q000737:chemistry* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D010455:Peptides; D016875:tau Proteins; D012694:Serine; D011392:Proline