title: Novel conformation-sensitive antibodies specific to three- and four-repeat tau.
abstract: Two types of tau isoform, three- and four-repeat tau, are found in neurofibrillary tangles--a pathological hallmark of tauopathies. Which isoform is deposited in the affected tissues depends on the tauopathy. To study how and which tau isoforms contribute to neuronal degeneration, we have developed and characterized two novel conformation-sensitive antibodies, T3R and T4R. Two closely related synthetic peptides, PGGGKVQIVYK and PGGGSVQIVYK, respectively, were designed as antigens. The isoform-specific residues, (305)K in three-repeat tau or (305)S in four-repeat tau, and the PHF6 motif (VQIVYK) were identified as critical sequences. Despite the high similarity of the antigens, there was no cross-reactivity between T3R and T4R. Furthermore, T3R and T4R showed reduced binding to the thioflavin-positive beta-structural form of their target. These features may enable these antibodies to act as novel indicators that allow us to observe and evaluate conformational changes in each distinct isoform of tau.
authors.affiliation: Laboratory of Molecular Biology, The Graduate School of Environmental Health Sciences, Azabu University, 1-17-71 Fuchinobe, Sagamihara, Kanagawa, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Ueno
authors.forename: Ohoshi
authors.initials: O
authors.lastname: Murayama
authors.forename: Sumihiro
authors.initials: S
authors.lastname: Maeda
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Sahara
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Park
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murayama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sanda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Iwahashi
authors.forename: Motoo
authors.initials: M
authors.lastname: Matsuda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
mesh_terms: D001665:Binding Sites; D011485:Protein Binding; D011487:Protein Conformation; D016875:tau Proteins / Q000737:chemistry* / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D016875:tau Proteins