Abstract

We previously showed that the metal-binding domain 1–16 of intact amyloid-beta (Aβ) is involved in interactions with a number of proteins from the cytosolic fraction of SK-N-SH human neuroblastoma cells in a zinc-dependent manner only. It is known that hereditary mutations in the Aβ metal-binding domain (Aβ(1–16)), which accelerate the development of Alzheimer’s disease and post-translational modifications of amino acid residues, can significantly affect the domain’s structure in the presence of zinc ions. In this work, using the molecular fishing methodology for Aβ(1–16) isoforms with the Taiwanese mutation (D7H) and a phosphorylated Ser8 residue, proteins from the cytosol of SK-N-SH cells were found that are able to form zinc-dependent non-covalent complexes with these domains. The partner proteins identified for these isoforms differed from those for intact Aβ(1–16). In contrast, the Aβ(1–16) isoform with the English mutation (H6R) and the Aβ(1–16) isoform containing both an isomerized Asp7 residue and phosphorylated Ser8 residue did not interact with cytosolic proteins. The results are useful for developing methods for rational modulation of protein-protein interactions involving natural isoforms of beta-amyloid, and also indicate the possible role of beta-amyloid with phosphorylated Ser8 as a molecule involved in normal physiological processes.