A 31-residue peptide induces aggregation of tau's microtubule-binding region in cells.
Nat Chem
; 9(9): 874-881, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28837163
ABSTRACT
The self-propagation of misfolded conformations of tau underlies neurodegenerative diseases, including Alzheimer's. There is considerable interest in discovering the minimal sequence and active conformational nucleus that defines this self-propagating event. The microtubule-binding region, spanning residues 244-372, reproduces much of the aggregation behaviour of tau in cells and animal models. Further dissection of the amyloid-forming region to a hexapeptide from the third microtubule-binding repeat resulted in a peptide that rapidly forms fibrils in vitro. We show that this peptide lacks the ability to seed aggregation of tau244-372 in cells. However, as the hexapeptide is gradually extended to 31 residues, the peptides aggregate more slowly and gain potent activity to induce aggregation of tau244-372 in cells. X-ray fibre diffraction, hydrogen-deuterium exchange and solid-state NMR studies map the beta-forming region to a 25-residue sequence. Thus, the nucleus for self-propagating aggregation of tau244-372 in cells is packaged in a remarkably small peptide.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Células
/
Proteínas tau
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Agregação Patológica de Proteínas
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Agregados Proteicos
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Microtúbulos
Limite:
Humans
Idioma:
En
Revista:
Nat Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos