Effect of lipid environment on amyloid fibril formation of human serum amyloid A

• Published in: Chemistry and physics of lipids 2017-01, Vol.202, p.6-12
• Main Authors: Tanaka, Masafumi, Nishimura, Ayaka, Takeshita, Haruka, Takase, Hiroka, Yamada, Toshiyuki, Mukai, Takahiro
• Format: Article
• Language: English
• Subjects: Apolipoprotein; High-density lipoprotein; Humans; Lipid binding; Lipids - chemistry; Serum amyloid A; Serum Amyloid A Protein - chemistry
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2016.11.004

•Amyloid fibril formation of human serum amyloid A (SAA) under a lipid environment was investigated.•SAA (1–27) peptide bound to neutral and acidic, whereas SAA (43–63) peptide bound only to acidic lysophospholipids.•For both these SAA peptides, binding to lysophospholipids inhibited heparin-induced amyloid-like fibril formation.•Acidic lysophospholipids implied a possibility to promote fibril formation of SAA (1–27) peptide by themselves.•Amyloid fibril formation of SAA may be modulated by altering the lipid head group composition of HDLs during metabolism. 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.