title: Effect of lipid environment on amyloid fibril formation of human serum amyloid A.
abstract: Human serum amyloid A (SAA) is a precursor protein of AA amyloidosis and a component of high-density lipoproteins (HDLs), thus it is essential to investigate the amyloid fibril formation of SAA under a lipid environment. We used synthetic fragment peptides corresponding to the N-terminal (residues 1-27) and central (residues 43-63) regions of the SAA molecule, which are known to have amyloidogenic properties. Measurements of tryptophan fluorescence in conjunction with circular dichroism showed that SAA (1-27) peptide binds to neutral and acidic lysophospholipids, whereas SAA (43-63) peptide binds only to acidic lysophospholipids. For both these SAA peptides, binding to lysophospholipids inhibited heparin-induced amyloid-like fibril formation by stabilizing the α-helical structure. However, acidic lysophospholipids implied a possibility to promote fibril formation of SAA (1-27) peptide by themselves. These results suggest that the amyloid fibril formation of SAA may be modulated by altering the lipid head group composition of HDLs during metabolism.
authors.affiliation: Department of Biophysical Chemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan. Electronic address: masatnk@kobepharma-u.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Biophysical Chemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Nishimura
authors.affiliation: Department of Biophysical Chemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Takeshita
authors.affiliation: Department of Biophysical Chemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
authors.forename: Hiroka
authors.initials: H
authors.lastname: Takase
authors.affiliation: Department of Clinical and Laboratory Medicine, Jichi Medical University, Tochigi 329-0498, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Biophysical Chemistry, Kobe Pharmaceutical University, Kobe 658-8558, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mukai
mesh_terms: D006801:Humans; D008055:Lipids / Q000737:chemistry*; D000685:Serum Amyloid A Protein / Q000737:chemistry*
chemical_list: D008055:Lipids; D000685:Serum Amyloid A Protein
keywords: Apolipoprotein; High-density lipoprotein; Lipid binding; Serum amyloid A