title: Different associational and conformational behaviors between the second and third repeat fragments in the tau microtubule-binding domain.
abstract: The third repeat fragment (R3) in the four-repeat microtubule-binding domain of the water-soluble tau protein has been considered to play an essential role in the protein's filamentous assembly. To clarify the associational and conformational features that differentiate R3 from the second repeat, R2, the heparin-induced assembly profiles of these peptide fragments were monitored by the thioflavin fluorescence method and electron microscopy. The trifluoroethanol-induced reversible conformational change from a random structure to an alpha-helical structure, in an aqueous solution, was monitored by CD measurement, and the structure of R2 in trifluoroethanol solution was analyzed by a combination of two-dimensional 1H-NMR measurements and molecular modeling calculations to facilitate comparison with the structure of R3. The speed of R3 assembly was remarkably faster than that of R2, in spite of their similar amino acid sequences. The averaged NMR conformers of R2 exhibited the whole-spanning alpha-helical structure. Similar features observed in R2 and R3 conformers in trifluoroethanol were that the Leu10-Leu20/Lys20 sequence takes a helical structure with the amphipathic-like distribution of the respective side-chains, whereas the C-terminal moieties are both flexible. In contrast, a notable difference was observed at the N-terminal Val1-Lys6 sequence, namely, a helical conformation for R2 and an extended conformation for R3. These conformational behaviors would be associated with the different self-aggregation speeds and seeding reactions between R2 and R3.
authors.affiliation: Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan. minoura@gly.oups.ac.jp
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Minoura
authors.forename: Tian-Ming
authors.initials: TM
authors.lastname: Yao
authors.forename: Koji
authors.initials: K
authors.lastname: Tomoo
authors.forename: Miho
authors.initials: M
authors.lastname: Sumida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sasaki
authors.forename: Taizo
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016875:tau Proteins