title: Immunological and conformation characterization of a phosphorylated immunodominant epitope on the paired helical filaments found in Alzheimer's disease.
abstract: 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.
authors.affiliation: Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
authors.forename: E
authors.initials: E
authors.lastname: Lang
authors.forename: G I
authors.initials: GI
authors.lastname: Szendrei
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Otvos
mesh_terms: 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
chemical_list: D000939:Epitopes; D010446:Peptide Fragments; D010750:Phosphoproteins; D016875:tau Proteins