REVERSIBLE BETA-PLEATED SHEET FORMATION OF A PHOSPHORYLATED SYNTHETIC TAU-PEPTIDE

Serine416 of human τ protein is believed to be phosphorylated in Alzheimer neurofibrillary tangles. We synthesized a fragment of τ, consisting of amino acids 408-421 in both non-phosphorylated and serine416-phosphorylated forms. Circular dichroism in a trifluoroethanol-water mixture indicated a β-turn → β-pleated sheet conformational transition upon phosphorylation. The β-structure formation is intermolecular and can be inhibited by addition of Ca2+ ions or a phosphorylated tripeptide, but not with its non-phosphorylated analog. The presence of the phosphorylated τ peptide did not facilitate the formation of β-pleated sheets of a phosphorylated neurofilament fragment. Multivalent cations induced a conformational transition of this phosphorylated neurofilament peptide, but the effect was less specific than the transition induced in the τ fragment, and it could also be reversed with the competing phosphorylated tripeptide. © 1992 Academic Press, Inc.