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Solvent exposure of...
Solvent exposure of Tyr10 as a probe of structural differences between monomeric and aggregated forms of the amyloid-β peptide
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- Aran Terol, P. (författare)
- University Of Cambridge
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- Kumita, J.R. (författare)
- University Of Cambridge
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- Hook, S.C. (författare)
- University of Bristol,University Of Cambridge
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- Dobson, C.M. (författare)
- University Of Cambridge
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- Esbjörner Winters, Elin, 1978 (författare)
- University Of Cambridge,Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- Engelska.
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 468:4, s. 696-701
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https://doi.org/10.1...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Nyckelord
- Amyloid-β
- Aβ oligomer
- tyrosine fluorescence
- Acrylamide quenching
- Amyloid fibril
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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