1. Probing the amyloid-beta(1-40) fibril environment with substituted tryptophan residues.
- Author
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Touchette JC, Williams LL, Ajit D, Gallazzi F, and Nichols MR
- Subjects
- Amino Acid Sequence, Amyloid beta-Peptides metabolism, Benzothiazoles, Hydrophobic and Hydrophilic Interactions, Molecular Sequence Data, Peptide Fragments metabolism, Protein Structure, Secondary, Spectrometry, Fluorescence, Thiazoles metabolism, Amino Acid Substitution, Amyloid beta-Peptides chemistry, Amyloid beta-Peptides genetics, Peptide Fragments chemistry, Peptide Fragments genetics, Tryptophan
- Abstract
A signature feature of Alzheimer's disease is the accumulation of plaques, composed of fibrillar amyloid-beta protein (Abeta), in the brain parenchyma. Structural models of Abeta fibrils reveal an extensive beta-sheet network with a hydrophobic core extending throughout the fibril axis. In this study, phenylalanines in the Abeta(1-40) sequence were substituted with tryptophan residues at either position 4 (F4W) or 19 (F19W) to probe the fibril environment. The F4W substitution did not alter self-assembly kinetics, while the F19W change slightly lengthened the lag phase without hindering fibril formation. The tryptophan fluorescence of Abeta(1-40) F19W, but not Abeta(1-40) F4W, underwent a marked blue shift during fibril formation and this shift was temporally correlated with thioflavin T binding. Isolated Abeta(1-40) F19W fibrils exhibited the largest fluorescence blue shifts consistent with W19 insertion into the Abeta(1-40) fibril inner core and direct probing of the substantially hydrophobic environment therein., (2009 Elsevier Inc. All rights reserved.)
- Published
- 2010
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