title: Interplay between I308 and Y310 residues in the third repeat of microtubule-binding domain is essential for tau filament formation.
abstract: Investigation of the mechanism of tau polymerization is indispensable for finding inhibitory conditions or identifying compounds preventing the formation of paired helical filament or oligomers. Tau contains a microtubule-binding domain consisting of three or four repeats in its C-terminal half. It has been considered that the key event in tau polymerization is the formation of a β-sheet structure arising from a short hexapeptide (306)VQIVYK(311) in the third repeat of tau. In this paper, we report for the first time that the C-H⋯π interaction between Ile308 and Tyr310 is the elemental structural scaffold essential for forming a dry "steric zipper" structure in tau amyloid fibrils.
authors.affiliation: Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruto
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Minoura
authors.forename: Ryouhei
authors.initials: R
authors.lastname: Okuda
authors.forename: Taizo
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Yasuko
authors.initials: Y
authors.lastname: In
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishida
authors.forename: Koji
authors.initials: K
authors.lastname: Tomoo
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D007532:Isoleucine / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D008870:Microtubules / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D014443:Tyrosine / Q000737:chemistry; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure
chemical_list: C054369:MAPT protein, human; D050505:Mutant Proteins; D011994:Recombinant Proteins; D016875:tau Proteins; D007532:Isoleucine; D014443:Tyrosine