TY - JOUR
T1 - Probing the amyloid-β(1-40) fibril environment with substituted tryptophan residues
AU - Touchette, Jillienne C.
AU - Williams, Laura L.
AU - Ajit, Deepa
AU - Gallazzi, Fabio
AU - Nichols, Michael R.
PY - 2010/2
Y1 - 2010/2
N2 - A signature feature of Alzheimer's disease is the accumulation of plaques, composed of fibrillar amyloid-β protein (Aβ), in the brain parenchyma. Structural models of Aβ fibrils reveal an extensive β-sheet network with a hydrophobic core extending throughout the fibril axis. In this study, phenylalanines in the Aβ(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 Aβ(1-40) F19W, but not Aβ(1-40) F4W, underwent a marked blue shift during fibril formation and this shift was temporally correlated with thioflavin T binding. Isolated Aβ(1-40) F19W fibrils exhibited the largest fluorescence blue shifts consistent with W19 insertion into the Aβ(1-40) fibril inner core and direct probing of the substantially hydrophobic environment therein.
AB - A signature feature of Alzheimer's disease is the accumulation of plaques, composed of fibrillar amyloid-β protein (Aβ), in the brain parenchyma. Structural models of Aβ fibrils reveal an extensive β-sheet network with a hydrophobic core extending throughout the fibril axis. In this study, phenylalanines in the Aβ(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 Aβ(1-40) F19W, but not Aβ(1-40) F4W, underwent a marked blue shift during fibril formation and this shift was temporally correlated with thioflavin T binding. Isolated Aβ(1-40) F19W fibrils exhibited the largest fluorescence blue shifts consistent with W19 insertion into the Aβ(1-40) fibril inner core and direct probing of the substantially hydrophobic environment therein.
KW - Aggregation
KW - Amyloid-beta protein
KW - Fibrils
KW - Tryptophan fluorescence
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U2 - 10.1016/j.abb.2009.12.007
DO - 10.1016/j.abb.2009.12.007
M3 - Article
C2 - 19995549
AN - SCOPUS:75549090863
SN - 0003-9861
VL - 494
SP - 192
EP - 197
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -