Interplay between I308 and Y310 residues in the third repeat of microtubule-binding domain is essential for tau filament formation.
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.
Naruto
Keiko
K
Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
Minoura
Katsuhiko
K
Okuda
Ryouhei
R
Taniguchi
Taizo
T
In
Yasuko
Y
Ishida
Toshimasa
T
Tomoo
Koji
K
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
C054369:MAPT protein, human; D050505:Mutant Proteins; D011994:Recombinant Proteins; D016875:tau Proteins; D007532:Isoleucine; D014443:Tyrosine