FIBRIL FORMATION BY AN AMPHIPATHIC ALPHA-HELIX-FORMING POLYPEPTIDE PRODUCED BY GENE ENGINEERING

Citation
S. Kojima et al., FIBRIL FORMATION BY AN AMPHIPATHIC ALPHA-HELIX-FORMING POLYPEPTIDE PRODUCED BY GENE ENGINEERING, Proceedings of the Japan Academy. Series B Physical and biological sciences, 73(1), 1997, pp. 7-11
Citations number
34
Categorie Soggetti
Multidisciplinary Sciences",Biology
ISSN journal
03862208
Volume
73
Issue
1
Year of publication
1997
Pages
7 - 11
Database
ISI
SICI code
0386-2208(1997)73:1<7:FFBAAA>2.0.ZU;2-5
Abstract
The alpha(3)-peptide, which comprises three repeats of the seven-resid ue sequence Leu-Glu-Thr-Leu-Ala-Lys-Ala, was designed to form an amphi pathic alpha-helix with a hydrophobic surface by Leu residues and a hy drophilic surface by Glu and Lys residues, thus yielding a coiled coil or a helical bundle structure through their association. The alpha(3) -peptide was produced by gene engineering using Escherichia coli. Asso ciation to a tetramer had been demonstrated by sedimentation equilibri um analysis in a previous study. In addition to tetramerization, elect ron microscopic observation revealed that the alpha(3)-peptide formed ''fibrils'' 5 to 10 nm in width in 10 mM potassium phosphate/0.1 M KCl (pH 6.0). By increasing the salt concentration, the alpha(3)-peptide formed much larger ''fibers'' assembled from many ''filaments'' runnin g along the long axis, each of which was thinner and longer than those observed at lower salt concentration. Hydrophobic interaction is cons idered to be a main force responsible for forming the fibrous structur e. However, the electrostatic features of the alpha(3)-peptide seem to affect fibril assembly, since the shape and size of the fibrous struc ture were altered by the ionic strength of the solution. To our knowle dge, this is the first report to describe formation of a fibrous struc ture by a de novo designed alpha-helix-forming peptide, and thus the a lpha(3)-peptide with its simple sequence is considered to be a potenti al model peptide for investigating the molecular mechanisms of fibril formation by peptides or proteins.