Solvent exposure of Tyr10 as a probe of structural differences between monomeric and aggregated forms of the amyloid-β peptide
Artikel i vetenskaplig tidskrift, 2015

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.

tyrosine fluorescence

Amyloid fibril

Aβ oligomer

Amyloid-β

Acrylamide quenching

Författare

P. Aran Terol

University of Cambridge

J.R. Kumita

University of Cambridge

S.C. Hook

University of Cambridge

University of Bristol

C.M. Dobson

University of Cambridge

Elin Esbjörner Winters

Chalmers, Biologi och bioteknik, Kemisk biologi

Biochemical and Biophysical Research Communications

0006-291X (ISSN) 1090-2104 (eISSN)

Vol. 468 4 696-701

Ämneskategorier

Biologiska vetenskaper

DOI

10.1016/j.bbrc.2015.11.018