Defining lipid-binding regions of human serum amyloid A using its fragment peptides

Human serum amyloid A (SAA) protein is an apolipoprotein predominantly present in the high-density lipoprotein fraction of plasma. Despite its critical roles in lipid metabolism, especially in acute phases, systematic understanding of the lipid interaction of this protein is limited. Lipid-binding properties of synthetic fragment peptides corresponding to the N-terminal (residues 1–27), central (residues 43–63), and C-terminal (residues 77–104) parts of SAA molecule were examined. SAA (1–27) peptide binds to lipid forming an α-helical structure, whereas SAA (43–63) and (77–104) peptides do not display binding to lipid with any conformational changes. These results indicate that the N-terminal region of SAA is important for lipid interaction. In addition, the finding that deletion of or proline substitution in the most N-terminal region (residues 1–11) markedly decreased the binding to lipid further suggests that the α-helical structure in residues 1–11 is essential for lipid binding of SAA.