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dc.contributor.authorAran Terol, Pablo
dc.contributor.authorKumita, Janet R
dc.contributor.authorHook, Sharon C
dc.contributor.authorDobson, Christopher M
dc.contributor.authorEsbjörner, Elin K
dc.date.accessioned2015-11-11T17:21:57Z
dc.date.available2015-11-11T17:21:57Z
dc.date.issued2015-12-25
dc.identifier.citationBiochemical and Biophysical Research Communications 2015, 468(4): 696–701. doi:10.1016/j.bbrc.2015.11.018
dc.identifier.issn0006-291X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252592
dc.description.abstractAggregation 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.
dc.description.sponsorshipThis 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.
dc.languageEnglish
dc.language.isoen
dc.publisherElsevier BV
dc.rightsCreative Commons Attribution 4.0 International License
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectAmyloid-β
dc.subjectAβ oligomer
dc.subjectamyloid fibril
dc.subjecttyrosine fluorescence
dc.subjectacrylamide quenching
dc.titleSolvent exposure of Tyr10 as a probe of structural differences between monomeric and aggregated forms of the amyloid-β peptide.
dc.typeArticle
dc.description.versionThis is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.bbrc.2015.11.018
prism.endingPage701
prism.publicationDate2015
prism.publicationNameBiochem Biophys Res Commun
prism.startingPage696
prism.volume468
dc.rioxxterms.funderWellcome Trust
dcterms.dateAccepted2015-11-03
rioxxterms.versionofrecord10.1016/j.bbrc.2015.11.018
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2015-11-10
dc.contributor.orcidKumita, Janet [0000-0002-3887-4964]
dc.identifier.eissn1090-2104
rioxxterms.typeJournal Article/Review
cam.issuedOnline2015-11-10


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Creative Commons Attribution 4.0 International License
Except where otherwise noted, this item's licence is described as Creative Commons Attribution 4.0 International License