Special issue devoted to the E-MRS Symposium C “Peptide-based materials: from nanostructures to applications”, 7–11 June 2010, Strasbourg, France.
Impact on the replacement of Phe by Trp in a short fragment of Aβ amyloid peptide on the formation of fibrils†
Article first published online: 20 DEC 2010
Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.
Journal of Peptide Science
Special Issue: Peptide-based materials: from nanostructures to applications
Volume 17, Issue 2, pages 115–123, February 2011
How to Cite
Chaudhary, N. and Nagaraj, R. (2011), Impact on the replacement of Phe by Trp in a short fragment of Aβ amyloid peptide on the formation of fibrils. J. Peptide Sci., 17: 115–123. doi: 10.1002/psc.1339
- Issue published online: 13 JAN 2011
- Article first published online: 20 DEC 2010
- Manuscript Accepted: 7 NOV 2010
- Manuscript Revised: 1 NOV 2010
- Manuscript Received: 1 OCT 2010
- amyloid-forming peptide;
- aromatic interactions;
- peptide structure;
- peptide self-assembly
Aβ16–22 (Ac-KLVFFAE-NH2) is one of the shortest amyloid fibril-forming sequences identified in β-amyloid peptide. At neutral pH, the peptide forms fibrils in the concentration range of 0.2–2.0 mM after ≥ 10 days of incubation. Structures of the fibrils proposed based on solid-state NMR and MD simulations studies suggest antiparallel arrangement of β-strands and aromatic interactions between the Phe residues. In an effort to examine the role of aromatic interactions between two Phe residues in Aβ16–22, we have studied the self-assembly of Aβ16–22 (AβFF) and two of its variants, Ac-KLVFWAE-NH2 (AβFW) and Ac-KLVWFAE-NH2 (AβWF). The peptides were dissolved in methanol (MeOH) at a concentration of 1 mM and in water (AβFW and AβWF, 1 mM; AβFF, 330 µM). Peptide solutions (100 µM) were prepared in 50 mM sodium phosphate buffer at pH 7 by diluting from MeOH and water stock solutions. AβFW forms amyloid-like fibrils immediately from MeOH, as indicated by atomic force microscopy. Dilution of AβFW into phosphate buffer from stock solution prepared in MeOH results in fibrils, but with different morphology and dimensions. The secondary structure potentiated by MeOH seems to be important for the self-assembly of AβFW, as fibrils are not formed from water where the peptide is unordered. On the other hand, AβFF and AβWF do not form amyloid fibrils rapidly from any of the solvents used for dissolution. However, drying of AβWF from MeOH on mica surface gives rod-like and fibrous structures. Our study indicates that positioning of the aromatic residues F and W has an important role to play in promoting self-assembly of the Aβ16–22 peptides. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.