Fall 2009 » Research Briefs » Researchers Discover Additional Mechanism That Regulates Protein Activity

March, 2009

Roger Koeppe, University Professor of chemistry and biochemistry, and his colleagues have discovered a new mechanism that regulates
the interaction of proteins in cell membranes. This discovery may lead to more efficient drug screening and possibly different methods for fighting infections.

The researchers reported their findings in the journal Nature.

Scientists have explained the interaction of antibiotics using a "lock and key" model, where a small drug of a certain shape (the key) binds to a bacterial protein (the lock) to neutralize it and prevent the spread of an infection.

In the Nature paper, the researchers show that this model is not
the only rule in drug-protein interaction. They discovered that the mirror image of a peptide isolated from tarantula venom had the same effect on a certain type of pressure-sensitive cell membrane protein channel as did the natural peptide toxin - a finding that violates the "lock and key" model because the toxin and its mirror image have
different shapes.

Further, they found that the mirror images of bacterial gramicidin channels, developed in the Koeppe laboratory, respond much like
natural gramicidin channels to both the tarantula toxin and its mirror image. "The effect is similar in different chemical systems," Koeppe said. The researchers have concluded that, instead of working by the traditional "lock and key" model, the peptide toxin and its mirror image change the shape or curvature of the lipid bilayer, or the protective "skin" of the cell membrane.

This finding opens up a host of new applications, including the possibility of using mirror-image proteins for drug therapies. Often, the mirror-image peptides or proteins are biologically more stable and, if developed into drugs, could last longer in the body, Koeppe said. Also, the mirror-image proteins don't activate the body's immune system as effectively, which could have a positive impact on organ transplant acceptance.

The gramicidin channel system also could be used to screen the generalized effects of potential drugs on the mechanical properties of lipid bilayer membranes.

"If new drugs could be tested on gramicidin channels, it could speed up predictions of what such drugs would do in other systems," Koeppe said. "This could help companies find out early if there is a problem instead of investing three years and then finding out."