title: Structural requirement of fibrogenic laminin-derived peptide A119 (LSNIDYILIKAS) for amyloid-like fibril formation and cellular activity.
abstract: A119 peptide (LSNIDYILIKAS), derived from the mouse laminin α1 chain sequence (residues 1321-1332), promotes cell attachment, neurite outgrowth, and amyloid-like fibril formation. In this study, we evaluated the structural requirements of A119 for biological activities and amyloid-like fibril formation. The attachment of the cell to A119 was inhibited by heparin, and using syndecan- and glypican-overexpressed cells, it was determined that A119 specifically binds to syndecans. We also evaluated the critical residues for A119 activities using a set of alanine-substituted peptides. Cell attachment activity was significantly reduced in the Leu(1)-, Ser(2)-, Asn(3)-, Ile(4)-, Ile(7)-, Ile(9)-, and Lys(10)-substituted alanine peptides. Residues Ile(4), Ile(7), Ile(9), and Lys(10) were important for neurite outgrowth activity. Congo red staining and electron microscopic examination revealed that the Ile(4), Ile(7), Ile(9), and Ser(12) residues of A119 were required for amyloid-like fibril formation. These data suggest that the Ile residues are critical for the amyloid-like fibril formation, cell attachment, and neurite outgrowth activity of A119. Furthermore, an enantiomer of A119 showed similar amyloid-like fibril formation and increased levels of cell attachment and FAK signal transduction. These findings shed light on the mechanism of amyloid-like fibril formation and demonstrate a relationship between the ability to form amyloid-like fibrils and cell behavior.
authors.affiliation: Laboratory of Clinical Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Katagiri
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takeyama
authors.forename: Kentaro
authors.initials: K
authors.lastname: Hozumi
authors.forename: Yamato
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: Motoyoshi
authors.initials: M
authors.lastname: Nomizu
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000096:biosynthesis*; D002478:Cells, Cultured; D006801:Humans; D007797:Laminin / Q000737:chemistry* / Q000378:metabolism; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D000682:Amyloid; D007797:Laminin; D010446:Peptide Fragments