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May 2, 2002

Electronic newsroom

02-34

 

Looking for Clues About How Proteins Talk to Each Other

UPTON, NY — Proteins perform distinct and very well-defined tasks, but little is known about how interactions among them are structured at the cellular level. Now, two physicists reveal that — at least in yeast cells — these interactions are not random, but well organized. This result is published in the May 3, 2002 issue of Science.

“Although scientists understand how a given protein interacts with other proteins, the way they connect with each other as a whole remains mysterious,” says Sergei Maslov, a physicist at the U.S. Department of Energy’s Brookhaven National Laboratory, one of the study’s two authors.

For the last 10 years, Maslov, an expert in statistical physics, has been studying complex systems such as collections of particles, proteins, and networked computers. In the new study, Maslov and physicist Kim Sneppen of the Norwegian University of Science and Technology used computer modeling to look at how proteins interact with each other.

Although scientists know that some proteins are very busy “talking” to many other proteins, Maslov and Sneppen discovered that such highly connected proteins are unlikely to “talk” to each other. To illustrate this intriguing phenomenon, Maslov uses the analogy of airline “hubs.”

“Each airline company has a network of flights connecting different cities,” he says. “But when a city serves as a hub for one company, the neighboring cities are mostly served by this company. Also, the hub is served mainly by this company and not by another big company. So the two big companies rarely ‘talk’ to each other.”

The network of 318 interactions among the 329 proteins that are present in the nucleus of yeast cells. Proteins are represented by dots and their interactions by lines. Maslov and Sneppen discovered that most of the neighbors of highly connected proteins have few neighbors themselves.
 

The scientists think that proteins interact this way to reduce interference among the messages of proteins that crisscross each other in the cell. The other possible advantage of this protein interaction pattern is to make the protein network inside the cell more stable. “Proteins with many connections seem not to want to be disturbed by wrong messages or anything ‘harmful’ to these proteins,” Maslov says.

To determine which among the 6,000 yeast proteins interact with each other, Maslov and Sneppen collected data on protein interactions in yeast cells from a public database. They then compared the resulting network of interactions to a simulated pattern — produced by a computer-modeling program — in which proteins interact randomly.

“If you took a given number of proteins and distributed interactions among them randomly, you would hardly find any particular protein that would have a lot of interactions. Proteins would all ‘talk’ randomly with each other in such a network,” Maslov says. “So, hubs of highly-interacting proteins are not something that you would expect to happen by pure chance.”

But the scientists did observe hubs of interacting proteins in the yeast cells. The connections between hub proteins reveal an “emergent property” that acts beyond the level of the functions of the individual proteins and makes them act together to coordinate their functions. Studying these interactions can help identify these coordinated functions, and may also reveal intrinsic features of the interacting proteins.

The “holistic” approach taken by Maslov is part of an ongoing interdisciplinary effort in which scientists are trying to understand phenomena involving many proteins, such as diseases. The understanding of how protein interaction networks are designed might, for instance, help scientists better understand the causes of cancer. One of the hubs in the human protein network, called p53, has a major role in preventing cells from developing into a tumor.

“The computer modeling program developed in this work can be applied to interactions in other networks such as food webs in ecosystems, neural networks, the Internet, and even among stock market agents,” Maslov says.

This work was funded by the U.S. Department of Energy’s Office of Science, which supports basic research in a variety of scientific fields.

The U.S. Department of Energy's Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies. Brookhaven also builds and operates major facilities available to university, industrial, and government scientists. The Laboratory is managed by Brookhaven Science Associates, a limited liability company founded by Stony Brook University and Battelle, a nonprofit applied science and technology organization.