João Carlos Marcos

Centro de Química
Universidade do Minho

7 Junho 2019

Short-Talk: Inhibition of protein aggregation by poly(ethylene glycol)

The aggregation of proteins is a widely distributed phenomenon that has serious implication in the onset of several patologies like Alzheimer, Parkinson and Huntington’s diseases or spongiform encephalopaties. In most cases, this happens due to the unfolding or misfolding of specific proteins. These altered protein conformations expose hydrophobic patches that interact with each other leading to the formation of pathological aggregates. Understanding the mechanism of protein unfolding, misfolding and aggregation is thus of fundamental importance to unveil the processes that trigger these diseases, and may pave the way to the design of drugs against them. Some compounds are known to reduced or eliminate protein aggregation. For instance poly(ethylene glycol) (PEG) has been described to have contradictory effects on protein stabilization. Here we used myoglobin as a model protein to further explore the effects of PEG on proteins thermal denaturation and aggregation. It was found that although this polymer reduces the protein thermal stability it increases significantly the reversibility of protein folding reaching a limit that is close to 100% in the presence of PEG 3350. The effect seems to be related to the concentration of polymer monomers and suggest that PEG interacts with myoglobin preventing its irreversible aggregation. Molecular dynamics simulations studies further corroborate this hypothesis.