Requirement of Ala residues at g position in heptad sequence of α-helix-forming peptide for formation of fibrous structure

One feature of the alpha 3-peptide, which has the amino acid sequence of (Leu-Glu-Thr-Leu-Ala-Lys-Ala)(3), that distinguishes it from many other alpha-helix-forming peptides is its ability to form fibrous assemblies that can be observed by transmission electron microscopy. In this study, the effects of Ala -> Gln substitution at the e (5th) or g (7th) position in the above heptad sequence of the alpha 3-peptide on the formation of alpha-helix and fibrous assemblies were investigated by circular dichroism spectral measurement and atomic force microscopy. The 5Q alpha 3-peptide obtained by Ala -> Gln substitution at the e position of the alpha 3-peptide was found to form very short fibrils with long- elliptical shape, whereas the 7Q alpha 3-peptide with Gln residues at the g position lost its ability to form such assemblies, in spite of alpha-helix formation in both peptides; the stabilities of both peptides decreased. These results indicate that Ala residues at the g position in the heptad sequence of the alpha 3-peptide are key residues for the formation of fibrous assemblies, which may be due to hydrophobic interactions between alpha-helical bundle surfaces.