Amyloid‑β “Co-assembles” with Coatomer Subunit Delta (δ-COP)

Previous studies
showed that δ-COP interacts with APP and
regulates its intracellular trafficking, while an important reduction
in the level of Aβ plaques was observed in AD/δ-COP I422T
mice. Here, we show that δ-COP interacts directly with Aβ
assemblies according to experiments and simulations. Experiments suggest
a two-binding site model, one with high affinity and one with lower
affinity. Simulations comply with experiments and provide mechanistic
biophysical insights into the high-affinity interactions, comprising
a “co-assembly-like” β-sheet interaction within
nearly identical domains 426DGEYRHDS433 of δ-COP
and 1DAEFRHDS8 of Aβ, complemented by
interactions between 416GVGAPVIGEI425 of δ-COP
and 13HHQKLVFFAED23 of Aβ, with a β-bridge
between δ-COP I422 and Aβ D23. As such, our simulations
highlight the role of I422, which is also investigated in comparison
to T422. Our studies can provide impetus for the future investigation
of the interaction between δ-COP and Aβ, particularly
in its involvement in intracellular trafficking in Alzheimer’s
disease.