By using brightly hued dyes, George Mason University researchers discovered an innovative way to reveal where proteins touch each other, possibly leading to new treatments for cancer, arthritis, heart disease and even lung disease.
Nature Communications published the study today. This research was funded by a grant from the National Institutes of Health Innovative Molecular Analysis Technologies Program.
George Mason researchers unraveled the mystery of deciphering the contact points where proteins touch each other. "One protein interlocks with another protein like adjacent pieces in a jigsaw puzzle, and this sends a signal down the line to the next protein," says Lance Liotta, co-director of the Mason-based Center for Applied Proteomics and Molecular Medicine.
The mystery is in the "hot spots" where proteins interlock. Researchers know which proteins connect but couldn't pinpoint where it happens. Until now, thanks to Mason's newly published approach.
Dyes -- the type used in common copying machines and textiles -- are mixed with proteins. The dye paints the proteins everywhere except where the proteins are connected to one another. Then the proteins are disconnected but the dye remains, excluding the blank spot where the proteins were "kissing."
Finding ways to break up interlocking proteins could be used to locate new drug targets, says Virginia "Ginny" Espina, a professor with the center. Pharmaceutical companies could use the Mason-developed process to create drugs that break up the protein-to-protein connection or stop it from happening altogether, she says.
The team tackled a complex interaction of three proteins, called interleukin signaling, that leads to painful inflammatory arthritis and other diseases including inflammatory bowel disease. They created two inhibitors -- a peptide and an antibody -- that broke up the protein connection in a test tube. "Both inhibitors made these proteins fall apart and they couldn't send out a signal for inflammation," Liotta says.
Until the Mason-led advancement, researchers have struggled to figure out where proteins make contact. "It seems very easy but, in reality, it's not," says Alessandra Luchini, a professor with the proteomics center who created the experimental method. Researchers have used computer modeling and crystalized proteins but couldn't show proteins making contact in real time, she says. "Using this tool, we now can study the protein exactly as it's found in nature," Luchini says.
And as it turns out, the printer dyes not only paint a pretty picture, but they are the perfect size to color the proteins -- and they stick. The Mason team is using blue, red, purple and orange dyes.
The inspiration for the groundbreaking research happened two years ago while Espina and Liotta were driving on the Washington, D.C., Beltway from their respective homes in Maryland to the lab on Mason's Prince William Campus. During their daily conversation, Espina mentioned she had read a paper about how dyes were used to paint chromosomes, and she wondered if a similar approach could be used for proteins.
A few months later, after a conference in Ireland, they picked up the conversation. "We were brainstorming how to solve this problem," Espina says. "Alessandra then designed the experiment, starting with this far-flung idea."After painting the proteins with the dyes, she used a protein analysis method called mass spectrometry to read out the points where the proteins connected.
That far-flung idea solved the problem of identifying where proteins touch each other, and has led to a novel method to find new classes of treatments.
- Alessandra Luchini, Virginia Espina, Lance A. Liotta. Protein painting reveals solvent-excluded drug targets hidden within native protein–protein interfaces. Nature Communications, 2014; 5 DOI: 10.1038/ncomms5413
Cite This Page: