Abstract Human serum amyloid A (SAA) is an apolipoprotein that predominantly associates with high-density lipoprotein (HDL) in the blood and participates in lipid metabolism. In addition, SAA serves as a precursor of amyloid fibrils that contribute to the development of AA amyloidosis. Chemical modifications of amyloidogenic proteins can influence the formation of amyloid fibrils. Recently, various modified SAA molecular species have been discovered in patients with AA amyloidosis. In the present study, we examined how carbamoylation and oxidation affect the structural stability, lipid binding, and amyloid fibril formation of SAA. Thermal denaturation experiments showed that these modifications reduced the thermal stability of the SAA molecule at low temperatures, although SAA itself is unstructured at physiological temperature. Upon binding to phospholipid vesicles, α-helical structure was induced. Carbamoylation exerted minimal effects on the lipid binding, whereas oxidation markedly reduced it. Chemical modifications affected not only the kinetics of amyloid fibril formation but also their fibril morphologies. Overall, these findings suggest that chemical modifications of SAA can alter its structural stability, lipid-binding ability, and amyloidogenic properties, thereby potentially contributing to the onset of AA amyloidosis.
Tanaka et al. (Fri,) studied this question.
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