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Impact on the replacement of Phe by Trp in a short fragment of Aβ amyloid peptide on the formation of fibrils
Author(s) -
Chaudhary Nitin,
Nagaraj Ramakrishnan
Publication year - 2011
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1339
Subject(s) - fibril , chemistry , peptide , antiparallel (mathematics) , amyloid fibril , amyloid (mycology) , crystallography , methanol , amyloid β , stereochemistry , biophysics , biochemistry , organic chemistry , inorganic chemistry , medicine , physics , disease , pathology , quantum mechanics , magnetic field , biology
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 m M 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 m M and in water (AβFW and AβWF, 1 m M ; AβFF, 330 µ M ). Peptide solutions (100 µ M ) were prepared in 50 m M 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. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.