Catalytic activity of copper ions in the amyloid fibrillation of b-lactoglobulin

The self-assembly of proteins and polypeptides in amyloid fibrillar aggregates is rapidly emerging as a promising route towards the fabrication of nano-objects with controlled morphologies and properties. Transition metal ions are known to play an important but elusive role in the amyloid fibrillation associated with neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. We have considered the effect of copper ions Cu2+ on the nanoscale morphology and fibrillation kinetics of b-lactoglobulin (bLG), a model protein not related to amyloid diseases, which denatures and selfassembles in nanofibrils upon heating at low pH and ionic strength. We found that an increasing level of Cu2+ decreases the enthalpy of denaturation and significantly increases the rate of fibril nucleation, also producing a small increase of the fibril elongation rate. Cu2+ acts as a catalytic agent during protein denaturation and fibrillation, without binding to bLG before or after heating, and produces only minor changes in fibril morphology. Beside possible implications for amyloid pathologies in vivo, our results suggest that transition metal ions can be used to control the self-assembly of protein-based nanoobjects in vitro.