Keeping proteins active outside of the cell

Christopher DelRe and Charley Huang

A METHOD has been developed for keeping proteins functional in non-native environments, which could be used to create protein “mats” that can soak up chemical pollution.

Keeping proteins alive outside of cells and combining them with synthetic components has proven to be difficult. Proteins removed from their natural environment can fall apart or the activity of the protein can be hampered. The surfaces of proteins are chemically diverse and heterogeneous, and they often need to fold into a specific structure with the help of other proteins. Protein folding can become affected when a homopolymer is conjugated to the protein surface and this will deform the protein chain. In nature, disordered proteins can fix this problem by adopting local chain conformation. Researchers have now developed a synthetic heteropolymer that can mimic natural disordered proteins and therefore stabilise the proteins that have been removed from their cells.

They designed a heteropolymer, called RHP, which is comprised of four methacrylate-based monomers in order to give it as much chemical diversity as possible. RHP increases protein folding and also solubilises membrane proteins in aqueous solutions.

They tested the functionality of the RHP by combining it with organophosphorus hydrolase (OPH), which is an enzyme that can degrade the organophosphates that are commonly used as insecticides and chemical warfare agents. OPH easily becomes inactive and organophosphates have poor solubility in aqueous solution, therefore there is a need to retain the OHP activity while it is in a solution with organophosphates. The researchers tested the OHP activity with a common pesticide, methyl parathion (MP) and found that RHP/OPH retains 80% of the initial OPH activity after 24 hours because RHP can stabilise OHP in aqueous and organic media. This ability can be used to create protein “mats” that are capable of soaking up and trapping chemical pollution.

"Proteins have very well-defined statistical patterns, so if you can mimic that pattern, then you can marry the synthetic and natural systems, which allows us to make these materials," said study author Ting Xu from the University of California Berkeley. "Our study indicated that the approach should be applicable to other enzymes. This may make it possible to have a portable chemistry lab in different materials." 

Science http://doi.org/cmrz