Effect of Cu2+ and Zn2+ Ions on Human Serum Albumin Interaction with Plasma Unsaturated Fatty Acids

Document Type

Article

Publication Date

2019

Keywords

ADAlzheimer's disease, Alzheimer's disease, Aβamyloid β peptide, amyloid β peptide, HSAhuman serum albumin, human serum albumin, ndHSAhuman serum albumin prepared under non-denaturing conditions using affinity chromatography, purchased from Merck KGaA (#126654), human serum albumin prepared under non-denaturing conditions using affinity chromatography, purchased from Merck KGaA (#126654), FAfatty acid, fatty acid, LAlinoleic acid, linoleic acid, OAoleic acid, oleic acid, ArAarachidonic acid, arachidonic acid, DHAdocosahexaenoic acid, docosahexaenoic acid, CACcritical aggregation concentration, critical aggregation concentration, nmaxfatty acid binding capacity of HSA, fatty acid binding capacity of HSA, bis-ANS4, 4′-dianilino-1, 1′-binaphthyl-5, 5′-disulfonic acid, 4, 4′-dianilino-1, 1′-binaphthyl-5, 5′-disulfonic acid, Serum albumin, Fatty acid, Copper, Zinc, Protein-lipid interaction, Protein-ligand interaction

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.ijbiomac.2019.03.085

Abstract

Human serum albumin (HSA) serves as a depot and carrier of multiple unrelated ligands including several participants of the pathogenesis of Alzheimer's disease (AD), such as amyloid β peptide (Aβ), Zn2+/Cu2+ ions, docosahexaenoic (DHA), linoleic (LA), and oleic (OA) acids. To explore the interplay between HSA interaction with Zn2+/Cu2+ and the plasma unsaturated fatty acids (DHA, LA, OA, and arachidonic acid (ArA)), we have studied the metal dependence of the fatty acid (FA) binding capacity of HSA (nmax) and structural consequences of the HSA-FA interactions. HSA loading with Zn2+ decreases nmax value by 0.3–1.5, while its saturation with Cu2+ causes the FA-dependent nmax changes by up to 0.9. The Cu2+-induced decline in nmax value for DHA is due to conformational rearrangements in HSA molecule. In other cases, the changes in nmax are attributed to steric hindarance/facilitation of the HSA-FA interaction because of the protein multimerization/monomerization, as confirmed by chemical crosslinking. The surface hydrophobicity of HSA is Cu2+-, Zn2+-, and FA-dependent and decreases upon the FA binding, according to bis-ANS fluorescence data. Overall, Zn2+ or Cu2+ binding selectively affect HSA interaction with the FAs studied, in part due to changes in quaternary structure of the protein.

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Citation / Publisher Attribution

International Journal of Biological Macromolecules, v. 131, p. 505-509

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