title: Impact on the replacement of Phe by Trp in a short fragment of Aβ amyloid peptide on the formation of fibrils.
abstract: Aβ(16-22) (Ac-KLVFFAE-NH(2) ) 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 Aβ(16-22) , we have studied the self-assembly of Aβ(16-22) (AβFF) and two of its variants, Ac-KLVFWAE-NH(2) (AβFW) and Ac-KLVWFAE-NH(2) (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 Aβ(16-22) peptides.
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India.
authors.forename: Nitin
authors.initials: N
authors.lastname: Chaudhary
authors.forename: Ramakrishnan
authors.initials: R
authors.lastname: Nagaraj
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D018625:Microscopy, Atomic Force; D010649:Phenylalanine / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D010649:Phenylalanine; D014364:Tryptophan