title: The role of histidines in amyloid β fibril assembly.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Brännström
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Sweden.
authors.forename: Tohidul
authors.initials: T
authors.lastname: Islam
authors.affiliation: Department of Molecular Biology, Umeå University, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Sandblad
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Olofsson
mesh_terms: D019943:Amino Acid Substitution; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000378:metabolism* / Q000473:pathology; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020349:Surface Plasmon Resonance
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; C078592:amyloid beta-protein (1-40); D006639:Histidine
keywords: abeta; amyloid; fibril; histidine; stability; surface plasmon resonance