N-terminal truncation of peptide effects on human serum albumin and beta amyloid peptide interaction

Abstract

More than half of the beta-amyloid interactions in cerebrospinal fluid are with human serum albumin (HSA). For a number of reasons, including the transient nature of beta-amyloid peptides, the high molecular weight of beta-amyloid peptide relative to other ligands, and the longer length of beta-amyloid peptide than other ligands, the study of the interaction of this peptide with HSA is challenging. Here, the interaction of 42-residue beta-amyloid (Aβ1−42) and its two N-terminal truncated forms, Aβ4−42 and Aβ5−42, with HSA has been studied by molecular docking method. From each docking, the residues involved in the interaction of beta amyloid peptides with HSA were determined. Beta-amyloid acts like fatty acids in binding to HSA. In general, both the A and B chains and I and III domain of each chain are involved in the interaction of HSA with the peptides. The solvent accessible surface area of the beta amyloid peptides residues, the distance between the side chain of lysine-28 and the side chain of alanine-42 and the position of the Phe19, Ile31 and Leu34 were determined to compare docking results with experimental evidences. Analysis of the results obtained for these quantities shows that HSA reduces the tendency for beta-amyloid aggregation.