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Probing the amyloid-beta(1-40) fibril environment with substituted tryptophan residues.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 2010 Feb 15; Vol. 494 (2), pp. 192-7. Date of Electronic Publication: 2009 Dec 06. - Publication Year :
- 2010
-
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.<br /> (2009 Elsevier Inc. All rights reserved.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1096-0384
- Volume :
- 494
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 19995549
- Full Text :
- https://doi.org/10.1016/j.abb.2009.12.007