Solvent exposure of Tyr10 as a probe of structural differences between monomeric and aggregated forms of the amyloid-β peptide.
Publication Date
2015-12-25Journal Title
Biochem Biophys Res Commun
ISSN
0006-291X
Publisher
Elsevier BV
Volume
468
Pages
696-701
Language
English
Type
Article
Metadata
Show full item recordCitation
Aran Terol, P., Kumita, J., Hook, S. C., Dobson, C., & Esbjörner, E. K. (2015). Solvent exposure of Tyr10 as a probe of structural differences between monomeric and aggregated forms of the amyloid-β peptide.. Biochem Biophys Res Commun, 468 696-701. https://doi.org/10.1016/j.bbrc.2015.11.018
Abstract
Aggregation of amyloid-β (Aβ) peptides is a characteristic pathological feature of Alzheimer's disease. We have exploited the relationship between solvent exposure and intrinsic fluorescence of a single tyrosine residue, Tyr10, in the Aβ sequence to probe structural features of the monomeric, oligomeric and fibrillar forms of the 42-residue Aβ1-42. By monitoring the quenching of Tyr10 fluorescence upon addition of water-soluble acrylamide, we show that in Aβ1-42 oligomers this residue is solvent-exposed to a similar extent to that found in the unfolded monomer. By contrast, Tyr10 is significantly shielded from acrylamide quenching in Aβ1-42 fibrils, consistent with its proximity to the fibrillar cross-β core. Furthermore, circular dichroism measurements reveal that Aβ1-42 oligomers have a considerably lower β-sheet content than the Aβ1-42 fibrils, indicative of a less ordered molecular arrangement in the former. Taken together these findings suggest significant differences in the structural assembly of oligomers and fibrils that are consistent with differences in their biological effects.
Keywords
Amyloid-β, Aβ oligomer, amyloid fibril, tyrosine fluorescence, acrylamide quenching
Sponsorship
This work was funded by grants to E.K.E from the Wenner-Gren Foundations, the Hasselblad Foundation, and the Swedish Innovation Agency (Vinnova) and to C.M.D from the Wellcome Trust. The TEM imaging was carried out in the Multi-Imaging Unit in the Department of Physiology, Development and Neuroscience, University of Cambridge, UK and quantitative amino acid analysis was carried out at the Protein and Nucleic Acid Chemistry Facility, Department of Biochemistry, University of Cambridge, UK.
Identifiers
External DOI: https://doi.org/10.1016/j.bbrc.2015.11.018
This record's URL: https://www.repository.cam.ac.uk/handle/1810/252592
Rights
Creative Commons Attribution 4.0 International License
Licence URL: http://creativecommons.org/licenses/by/4.0/
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