Credit: © 2008 RSC

The primary structure of a protein — its amino acid sequence — dictates the way it folds into its native three-dimensional structure, which in turn gives it a characteristic function. Mistakes in this folding procedure, or processes by which correctly folded proteins unfurl to form other structures, lead to misfolded proteins that are responsible for diseases such as Alzheimer's, Creutzfeldt–Jakob disease, and bovine spongiform encephalopathy (mad-cow disease). There is, therefore, a need to develop systems that can return such proteins to their native structure. Vince Rotello and Mrinmoy De at the University of Massachusetts at Amherst have now shown1 that gold nanoparticles can be used to refold proteins to a structure close to their original native state and restore their function.

In separate experiments, cationic enzymatic proteins (α-chymotrypsin and papain) were denatured by heating — altering their structure, causing them to aggregate and significantly reducing their activity. Rotello and De functionalized the surface of gold nanoparticles with an organic acid and added them to the protein solutions. The nanoparticles electrostatically bound to cationic residues on the protein surface, which reduced protein–protein aggregation and enabled the protein to refold to its native state. The nanoparticles could be removed from the protein by exposing them to a salt solution that reduced the protein–particle electrostatic attraction.

The enzyme activity of the refolded α-chymotrypsin was restored to 93% of its original value and that of papain to 97%. The refolded structure was shown by circular dichroism to be much closer to the native state than to the denatured one, with many secondary structures such as helices, turns and random coils being regenerated.