A SERINE-]PROLINE CHANGE IN THE ALZHEIMERS DISEASE-ASSOCIATED EPITOPE TAU-2 RESULTS IN ALTERED SECONDARY STRUCTURE, BUT PHOSPHORYLATION OVERCOMES THE CONFORMATIONAL GAP

Monoclonal antibody Tau 2 was raised against bovine ti protein, was reported to to recognize a conformational epitope, and stainedτ was found in neurofibrillary tangles of Alzheimer's disease, but not normal human τ. 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 serene. 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 (β-pleated sheets characteristic of the neurofibrillary tangles. The spectra of the human peptide, its analog, β and the phosphorylated bovine sequence were very similar, featuring a weak, helical β-turn character. Eventual phosphorylation of epitopes of this otherwise heavily phosphorylated protein may overcome inter-species conformational gaps. © 1992.