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Effect of site-specific amino acid D-isomerization on β-sheet transition and fibril formation profiles of Tau microtubule-binding repeat peptides
- Tochio, Naoya, Murata, Takuya, Utsunomiya-Tate, Naoko
- Biochemical and biophysical research communications 2019 v.508 no.1 pp. 184-190
- Alzheimer disease, amino acids, animal tissues, brain, humans, patients, peptides, proteins
- d-amino acid-containing proteins have been found in several human tissues, and the spontaneous accumulation of d-amino acids in proteins is thought to be involved in age-dependent diseases including dementia. Tau, a microtubule-associated protein, is a major component of neurofibrillary tangles in Alzheimer's disease. Site-specific amino acid D-isomerization in Tau has been observed in the brains of patients with Alzheimer's disease. Here, we conducted amino acid D-isomerization at specific sites in microtubule-binding repeat peptides of Tau (Tau R2 and R3) and examined the effects on Tau structure and fibril formation. Our results demonstrate that amino acid D-isomerization in Tau R2 peptides decreased the rates of β-sheet transition and fibril formation compared with those of the wild-type peptide composed of all l-amino acids. In contrast, Tau R3 peptides that had undergone amino acid D-isomerization at either Asp314, Ser316, or Ser324 showed increased rates of β-sheet transition and fibril formation compared with those of the wild-type Tau R3 peptide.