Fatty Acids Compete with Aβ in Binding to Serum Albumin by Quenching Its Conformational Flexibility.

ABSTRACT: Human serum albumin (HSA) has been identified as an important regulator of amyloid-β (Aβ) fibrillization both in blood plasma and in cerebrospinal fluid. Fatty acids bind to HSA, and high serum levels of fatty acids increase the risk of Alzheimer's disease. In vitro, fatty-acid-loaded HSA (FA·HSA) loses the protective effect against Aβ fibrillization, but the mechanism underlying the interference of fatty acids on Aβ-HSA interactions has been unclear. Here, we used molecular dynamics simulations to gain atomic-level insight on the weak binding of monomeric Aβ40 and Aβ42 peptides with apo and FA·HSA. Consistent with recent NMR data, C-terminal residues of the Aβ peptides have the highest propensities for interacting with apo HSA. Interestingly, the Aβ binding residues of apo and FA·HSA exhi

SUBMITTER: Guo C 

PROVIDER: S-EPMC6349961 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature