Effect of site-specific amino acid D-isomerization on ß-sheet transition and fibril formation profiles of Tau microtubule-binding repeat peptides.
Biochem Biophys Res Commun
; 508(1): 184-190, 2019 01 01.
Article
em En
| MEDLINE
| ID: mdl-30471859
ABSTRACT
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 ß-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 ß-sheet transition and fibril formation compared with those of the wild-type Tau R3 peptide.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Proteínas tau
/
Aminoácidos
/
Microtúbulos
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article