A study from Indiana University has found evidence that extremely small changes in how atoms move in bacterial proteins can play a big role in how these microorganisms function and evolve.
The research, recently published in the Proceedings of the National Academy of Sciences, is a major departure from prevailing views about the evolution of new functions in organisms, which regarded a protein‘s shape, or “structure,” as the most important factor in controlling its activity.
“This study gives us a significant answer to the following question: How do different organisms evolve different functions with proteins whose structures all look essentially the same?” said David Giedroc, Lilly Chemistry Alumni Professor in the IU Bloomington College of Arts and Sciences’ Department of Chemistry, who is senior author on the study. “We’ve found evidence that atomic motions in proteins play a major role in impacting their function.”
The study also provides new insights into how microorganisms respond to their host’s efforts to limit bacterial infection. Serious bacterial infections in people include severe health-care-associated infections and tuberculosis, both of which have grown increasingly common over the past decade due to rising drug resistance in bacteria. About 480,000 people worldwide develop multidrug-resistant tuberculosis each year, for example, according to the Centers for Disease Control and Prevention.
“What we’ve shown is atomic-level motional disorder—or entropy—can impact gene transcription to affect the function of proteins in major ways, and that these motions can be ‘tuned’ evolutionarily,” said Daiana A. Capdevila, a postdoctoral researcher in Giedroc’s lab, who is first author on the study. “This may allow bacteria to rapidly evolve new ways to overcome medical treatment since atomic motions can be optimized for function more easily than a physical structure.”
In the battle between bacterial infection and modern medicine, she said a key step is “mapping” the enemy’s territory. Unraveling the molecular structure of proteins that trigger the mechanisms that thwart the human immune system informs the design of new drugs. However, this approach is based on the assumption that a protein’s shape fundamentally controls its behavior.
It also assumes proteins are rigid. The new study shows protein function is better understood by studying the structure’s internal atomic motion.
“This work is the clearest example thus far of the central and critical role that conformational entropy plays in protein…