title: Importance of local structures of second and third repeat fragments of microtubule-binding domain for tau filament formation.
abstract: To investigate the importance of the seventh residue of the second and third repeat fragments (R2 and R3 peptides) of the microtubule-binding domain (MBD) for tau filamentous assembly, the residues Lys and Pro were substituted (R2-K7P and R3-P7K). The filament formations of the R2 and R3 peptides were almost lost due to their substitutions despite their overall conformational similarities. The NOE analyses showed the importance of the conformational flexibility for the R2 peptide and the coupled extended and helical conformations for the R3 peptide in their limited N-terminal regions around their seventh residues. The result shows that the filament formation of MBD is initiated from a short fragment region containing the minimal conformational or functional motif.
authors.affiliation: Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Tokimasa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Minoura
authors.forename: Shuko
authors.initials: S
authors.lastname: Hiraoka
authors.forename: Koji
authors.initials: K
authors.lastname: Tomoo
authors.forename: Miho
authors.initials: M
authors.lastname: Sumida
authors.forename: Taizo
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishida
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D020449:Repetitive Sequences, Amino Acid; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D016875:tau Proteins