title: Structural stability of paired helical filaments requires microtubule-binding domains of tau: a model for self-association.
abstract: Highly purified and SDS-soluble paired helical filaments (PHFs) were immunogold labeled and immunoblotted with antibodies to tau: Tau 14 (N-terminal half), AH-1 (microtubule-binding domain), and Tau 46 (C-terminal end). The main component of PHFs was modified tau of 68, 64, and 60 kd, also called A68 or PHF-tau. Trypsin digestion reduced the maximum width of PHFs by 10%-20%, increased aggregation of filaments, and abolished the binding of Tau 14, but had no effect on the binding of AH-1. The smallest tau-reactive tryptic fragments were 13 and 7-8 kd, positive with AH-1, and negative with Tau 46. Our results and the model of Crowther and Wischik suggest that by self-association and anti-parallel arrangement of the microtubule-binding domains, PHF-tau forms the backbone of PHFs.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: H
authors.initials: H
authors.lastname: Ksiezak-Reding
authors.forename: S H
authors.initials: SH
authors.lastname: Yen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002918:Chymotrypsin / Q000378:metabolism; D000939:Epitopes; D006801:Humans; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009454:Neurofibrils / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D014357:Trypsin / Q000378:metabolism; D016875:tau Proteins
chemical_list: D000939:Epitopes; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D016875:tau Proteins; D002918:Chymotrypsin; D014357:Trypsin