Acceleration of amyloid fibril formation by carboxyl-terminal truncation of human serum amyloid A

Abstract Human serum amyloid A (SAA) is a precursor protein of AA amyloidosis. Although the full-length SAA is 104 amino acids long, the C-terminal-truncated SAA lacking mainly residues 77–104 is predominantly deposited in AA amyloidosis. Nevertheless, the amyloid fibril formation of such truncated forms of human SAA has never been investigated. In the present study, we examined the effect of C-terminal truncation on amyloid fibril formation of human SAA induced by heparan sulfate (HS). Circular dichroism (CD) measurements demonstrated that the C-terminal truncation induces a reduced α-helical structure of the SAA molecule. HS-induced increases in thioflavin T fluorescence for SAA (1–76) peptide and less significant increases for full-length SAA were observed. CD spectral changes of SAA (1–76) peptide but not full-length SAA were observed when incubated with HS, although the spectrum was not typical for a β-structure. Fourier transform infrared experiments clearly revealed that SAA (1–76) peptide forms a β-sheet structure. Transmission electron microscopy revealed that short fibrillar aggregates of SAA (1–76) peptides, which became longer with increasing peptide concentrations, were observed under conditions in which full-length SAA scarcely formed fibrillar aggregates. These results suggested that the C-terminal truncation of human SAA accelerates amyloid fibril formation.