Immunological and conformation characterization of a phosphorylated immunodominant epitope on the paired helical filaments found in Alzheimer's disease.
The immunological recognition pattern of one of the most commonly used monoclonal antibodies, PHF-1, which detects the paired helical filaments of Alzheimer's disease, exhibits a high degree of similarity with the recognition of a polyclonal antibody, anti-T3P, raised against a synthetic phosphopeptide, GAEIVYKS(Phospho)PVVSGD, corresponding to amino acids 389-402 of the microtubule-associated protein tau. A panel of 16 synthetic non-phosphorylated and phosphorylated peptides, excised from different regions of tau and peptide analogs thereof, were used to show that PHF-1 is indeed directed against the T3 fragment. Circular dichroism spectroscopy shows that the phosphorylated peptide exhibits a limited propensity to form intramolecular beta-pleated sheets, and alteration is found in the reverse-turn structure that dominates the middle section of the molecule. The shift in the turn-forming amino acids may also allow a stacking procedure, may interfere with microtubule assembly, and, consequently, may be accountable for deposit formation.
Lang
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E
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Szendrei
G I
GI
Lee
V M
VM
Otvos
L
L
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010750:Phosphoproteins / Q000737:chemistry* / Q000276:immunology; D011487:Protein Conformation; D016875:tau Proteins / Q000737:chemistry* / Q000276:immunology
D000939:Epitopes; D010446:Peptide Fragments; D010750:Phosphoproteins; D016875:tau Proteins