Probing the amyloid-β(1-40) fibril environment with substituted tryptophan residues

Jillienne C. Touchette, Laura L. Williams, Deepa Ajit, Fabio Gallazzi, Michael R. Nichols

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)192-197
Number of pages6
JournalArchives of Biochemistry and Biophysics
Issue number2
StatePublished - Feb 2010


  • Aggregation
  • Amyloid-beta protein
  • Fibrils
  • Tryptophan fluorescence


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