US chemists are going for gold to fold unravelled proteins. A team at the University of Massachusetts, Amherst, has demonstrated that anionic gold nanoparticles can be used to reorganise these biopolymers. 

Vincent Rotello and Mrinmoy De took their inspiration from nature. They studied natural biological chaperones, which are proteins with surfaces tailored to unfold and refold misfolded proteins, and had the idea to use nanoparticles as their synthetic equivalent. Rotello explains: 'Nanoparticles can be made in sizes consistent with biological chaperones and fine-tuned with a wide range of ligands.'  

Rotello and De used nanoparticles supporting carboxylate ligands to fold three denatured cationic proteins, -chymotryspin, papain and lysozyme. The gold nanoparticles promote protein refolding through electrostatic interactions between the exposed charged residues on the unfolded protein and the oppositely charged ligands on the gold nanoparticles. The overall high negative charge of the nanoparticle-protein complex prevents the proteins from aggregating and, by drawing the charged residues on the protein to its exterior, the nanoparticle promotes refolding. 

An unfolded protein can aggregate (top pathway) but anionic gold nanoparticles promote refolding instead (bottom pathway)

Previously, unfolded proteins have been refolded into their native form using surfactants or by changing the protein's environment. 'Prior approaches have generally targeted hydrophobic portions of the protein,' says Rotello. 'Our approach focuses on the charged residues, opening the possibility of refolding proteins intractable to other methods.'

Sam Gellman, an expert in protein folding at the University of Wisconsin, Madison, US, says the approach is 'a very creative and potentially versatile strategy for protein refolding. The use of nanoparticles as artificial chaperones is intriguing because their surface properties can be tailored in diverse ways.'

According to Rotello, protein misfolding is a common challenge in protein synthesis, as it complicates protein expression and purification. He asserts that the simplicity of this system makes it highly promising for this and related biotechnological applications. Gellman agrees. 'It will be interesting to see whether this technique can be used to refold proteins in chemically denatured states, as is often required in biotechnology,' he says.

Janet Crombie