Cargando…

The role of histidines in amyloid β fibril assembly

Low pH has a strong stabilising effect on the fibrillar assembly of amyloid β, which is associated with Alzheimer's disease. The stabilising effect is already pronounced at pH 6.0, suggesting that protonation of histidines might mediate this effect. Through the systematic substitution of the th...

Descripción completa

Detalles Bibliográficos
Autores principales: Brännström, Kristoffer, Islam, Tohidul, Sandblad, Linda, Olofsson, Anders
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5434815/
https://www.ncbi.nlm.nih.gov/pubmed/28267202
http://dx.doi.org/10.1002/1873-3468.12616
Descripción
Sumario:Low pH has a strong stabilising effect on the fibrillar assembly of amyloid β, which is associated with Alzheimer's disease. The stabilising effect is already pronounced at pH 6.0, suggesting that protonation of histidines might mediate this effect. Through the systematic substitution of the three native histidines in Aβ for alanines, we have evaluated their role in fibril stability. Using surface plasmon resonance, we show that at neutral pH the fibrillar forms of all His‐Ala variants are destabilised by a factor of 4–12 compared to wild‐type Aβ. However, none of the His‐Ala Aβ variants impair the stabilising effect of the fibril at low pH.