Investigation of the interaction of fusion Trx-Aβ40 proteins with heme

Abstract

Aβ amyloids (Aβ) are known for their key role in Alzheimer’s disease. There are two main species of Aβ – Aβ40 and Aβ42 – consisting of 40 and 42 amino acids, respectively. It has been previously shown that Aβ42 binds heme, and the resulting Aβ42-heme complex acts as a peroxidase. In this work we have tested whether the thioredoxin-Aβ40 (Trx-Aβ40) fusion protein binds heme and how they interact. His residues are known to be the best candidates to coordinate the iron of heme. We changed His codons of Aβ40 to other amino acid codons (Ala, Cys, Ser) to see whether a particular His residue is participating in a binding process. The heme binding experiments showed that mutants bind heme, but less efficiently than does Trx-Aβ40. Thus, it may be concluded as His residues participate in heme binding, but its full mechanism is still unclear. Also, we demonstrate that the Trx-Aβ40-heme complex functions as a peroxidase. Keywords: Aβ amyloids, heme, thioredoxin, mutants, peroxidase