title: Alzheimer-like paired helical filaments and antiparallel dimers formed from microtubule-associated protein tau in vitro.
abstract: Recent evidence from several laboratories shows that the paired helical filaments of Alzheimer's disease brains consist mainly of the protein tau in an abnormally phosphorylated form, but the mode of assembly is not understood. Here we use EM to study several constructs derived from human brain tau and expressed in Escherichia coli. All constructs or tau isoforms are rodlike molecules with a high tendency to dimerize in an antiparallel fashion, as shown by antibody labeling and chemical crosslinking. The length of the rods is largely determined by the region of internal repeats that is also responsible for microtubule binding. One unit length of the repeat domain (three or four repeats) is around 22-25 nm, comparable to the cross-section of Alzheimer PHF cores. Constructs corresponding roughly to the repeat region of tau can form synthetic paired helical filaments resembling those from Alzheimer brain tissue. A similar self-assembly occurs with the chemically cross-linked dimers. In both cases there is no need for phosphorylation of the protein.
authors.affiliation: Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wille
authors.forename: G
authors.initials: G
authors.lastname: Drewes
authors.forename: J
authors.initials: J
authors.lastname: Biernat
authors.forename: E M
authors.initials: EM
authors.lastname: Mandelkow
authors.forename: E
authors.initials: E
authors.lastname: Mandelkow
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli; D006801:Humans; D008854:Microscopy, Electron; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D011994:Recombinant Proteins; D016875:tau Proteins