10th international Biometals webinars

Mechanistic information of (dys)functional interactions between proteins and metals is important for the understanding of basic biology and to combat human diseases. In this talk, I will describe some of our latest biophysical research on the role of copper (Cu) ion homeostasis in disorders where proteins assemble into amyloid fibrils. Aggregation of the synaptic protein α-synuclein (aS) results in Lewy body deposits and degeneration of dopaminergic neurons in Parkinson’s disease (PD) patients. In addition to amyloids, hallmarks of PD (and of other amyloid diseases such as Alzheimer’s disease) include oxidative stress and, notably, Cu ion dys-homeostasis. aS is annotated as Cu-binding and in vitro work shows the aS monomer to bind Cu (in both redox states) tightly, but the biological relevance of Cu-binding to aS is not known. To begin to answer this question, we search for molecular links between Cu homeostasis proteins, Cu ions and aS amyloid formation. Here I will describe some of our recent results, for example on the interactions between (a) aS and the cytoplasmic Cu chaperone Atox1 as well as (b) Cu ions and aS amyloids. Increased knowledge of protein-copper cross-reactivity may eventually act as the basis for new drug discovery efforts.