Effect of C-terminal residues of Aβ on copper binding affinity, structural conversion and aggregation

Many properties of Aβ such as toxicity, aggregation and ROS formation are modulated by Cu²⁺. Previously, the coordination configuration and interaction of Cu²⁺ with the Aβ N-terminus has been extensively studied. However, the effect of Aβ C-terminal residues on related properties is still unclear. In the present study, several C-terminus-truncated Aβ peptides, including Aβ1-40, Aβ1-35, Aβ1-29, Aβ1-24 and Aβ1-16, were synthesized to characterize the effect of Aβ C-terminal residues on Cu²⁺ binding affinity, structure, aggregation ability and ROS formation. Results show that the Aβ C-terminal residues have effect on Cu²⁺ binding affinity, aggregation ability and inhibitory ability of ROS formation. Compared to the key residues responsible for Aβ aggregation and structure in the absence of Cu²⁺, it is more likely that residues 36-40, rather than residues 17-21 and 30-35, play a key role on the related properties of Aβ in the presence of Cu ²⁺.