Substituted tryptophans at amyloid-[beta](1-40) residues 19 and 20 experience different environments after fibril formation

Amyloid-[beta] protein (A[beta]) is the principal component of the neuritic plaques found in Alzheimer's disease. The predominant A[beta] morphology in the plaques is fibrillar which has prompted substantial in vitro work to better understand the molecular organization of A[beta] fibrils. In th...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics 2011-10, Vol.514 (1-2), p.27-32
Main Authors: McDonough, Ryan T, Paranjape, Geeta, Gallazzi, Fabio, Nichols, Michael R
Format: Article
Language:English
Subjects:
Acrylamide
Alzheimer's disease
Amyloid
Fibrillogenesis
Fibrils
Fluorescence
Hydrophobicity
Kinetics
Monomers
Neurodegenerative diseases
Plaques
Tryptophan
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Summary:Amyloid-[beta] protein (A[beta]) is the principal component of the neuritic plaques found in Alzheimer's disease. The predominant A[beta] morphology in the plaques is fibrillar which has prompted substantial in vitro work to better understand the molecular organization of A[beta] fibrils. In the current study, tryptophan substitutions were made at A[beta](1-40) position 19 (F19W) or 20 (F20W) to ascertain environmental differences between the two residues in the fibril structure. Kinetic studies revealed similar rates of fibril formation between A[beta](1-40) F19W and F20W and both peptides formed typical amyloid fibril structures. A[beta](1-40) F19W fibrils displayed a significant tryptophan fluorescence blue-shift in [lambda] sub(max (33 nm) compared to monomer while A[beta](1-40) F20W fibrils had a much smaller shift (9 nm). Fluorescence quenching experiments with water-soluble acrylamide and KI demonstrated that both W19 and W20 were much less accessible to quenching in fibrils compared to monomer. Lipid-soluble TEMPO quenched the fluorescence of A[beta](1-40) F19W fibrils more effectively than F20W fibrils in agreement with the fluorescence blue-shift results. These findings demonstrate distinct environments between A[beta](1-40) residues 19 and 20 fibrils and indicate that while W20 accessibility is compromised in A[beta] fibrils it resides in a much less hydrophobic environment than W19.)
ISSN:0003-9861
DOI:10.1016/j.abb.2011.07.018