Phoenix effect: Resurrected proteins double their natural activity

Denatured proteins often pile up to form toxic aggregates, which is the underlying reason for many illnesses such as Alzheimer, Parkinson and Huntington. Therefore the investigation of denaturation and renaturation mechanisms cannot be overestimated.

In a new study, David Avnir, professor at the Hebrew University in Jerusalem, and Vladimir Vinogradov, head of the International Laboratory of Solution Chemistry of Advanced Materials and Technologies at ITMO University, found that bringing proteins back to life is not only possible, but can be carried out with an improvement over their original activity.

This strange “Phoenix effect“ phenomenon owes to a new technique of protein renaturation based on combining thermally denatured proteins (carbonic anhydrase) with a colloid solution of inorganic aluminum oxide nanoparticles.

As the solution turns into a gel, the nanoparticles start binding together, exerting mechanical pressure on the protein molecules. As a result, each molecule ends up entrapped in its own individual porous shell, which prevents the malign process of protein aggregation and eventually restores their original spatial structure. Having compared the level of activity of proteins before denaturation and after renaturation, the chemists discovered that the resurrected ones were 180 percent more active than their native predecessors.

As professor David Avnir explains, one possible application of the discovery could help optimize the fabrication of drugs based on active proteins: "Some of the most effective drugs are based on active proteins that are harvested from cell cultures. However, from all proteins grown in such a way only 20 percent are native and suitable for use, while the remaining 80 percent are the so-called inclusion bodies, that is, non-functioning denatured proteins.