title: Effects of chain length of an amphipathic polypeptide carrying the repeated amino acid sequence (LETLAKA)(n) on α-helix and fibrous assembly formation.
abstract: Polypeptide α3 (21 residues), with three repeats of a seven-amino-acid sequence (LETLAKA)(3), forms an amphipathic α-helix and a long fibrous assembly. Here, we investigated the ability of α3-series polypeptides (with 14-42 residues) of various chain lengths to form α-helices and fibrous assemblies. Polypeptide α2 (14 residues), with two same-sequence repeats, did not form an α-helix, but polypeptide α2L (15 residues; α2 with one additional leucine residue on its carboxyl terminal) did form an α-helix and fibrous assembly. Fibrous assembly formation was associated with polypeptides at least as long as polypeptide α2L and with five leucine residues, indicating that the C-terminal leucine has a critical element for stabilization of α-helix and fibril formation. In contrast, polypeptides α5 (35 residues) and α6 (42 residues) aggregated easily, although they formed α-helices. A 15-35-residue chain was required for fibrous assembly formation. Electron microscopy and X-ray fiber diffraction showed that the thinnest fibrous assemblies of polypeptides were about 20 Å and had periodicities coincident with the length of the α-helix in a longitudinal direction. These results indicated that the α-helix structures were orientated along the fibrous axis and assembled into a bundle. Furthermore, the width and length of fibrous assemblies changed with changes in the pH value, resulting in variations in the charged states of the residues. Our results suggest that the formation of fibrous assemblies of amphipathic α-helices is due to the assembly of bundles via the hydrophobic faces of the helices and extension with hydrophobic noncovalent bonds containing a leucine.
authors.affiliation: Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takei
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imada
authors.forename: Keiichi
authors.initials: K
authors.lastname: Namba
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
authors.forename: Yukino
authors.initials: Y
authors.lastname: Kuriki
authors.forename: Masakuni
authors.initials: M
authors.lastname: Yoshino
authors.forename: Kazumori
authors.initials: K
authors.lastname: Yazaki
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kojima
authors.forename: Tsunetomo
authors.initials: T
authors.lastname: Takei
authors.forename: Takuya
authors.initials: T
authors.lastname: Ueda
authors.forename: Kin-ichiro
authors.initials: K
authors.lastname: Miura
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D057927:Hydrophobic and Hydrophilic Interactions; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D020449:Repetitive Sequences, Amino Acid; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D010455:Peptides