A collaborative team of scientists including biochemist Peter Chien at the University of Massachusetts Amherst has reconstructed how bacteria tightly control their growth and division, a process known as the cell cycle, by specifically destroying key proteins through regulated protein degradation. Regulated protein degradation uses specific enzymes called energy dependent proteases to selective destroy certain targets. Because regulated protein degradation is critical for bacterial virulence and invasion, understanding how these proteases function should help to uncover pathways that can be targeted by new antibiotics.

All organisms use controlled degradation of specific proteins to alter cellular behavior in response to internal or external cues, says Chien, an assistant professor of biochemistry and molecular biology. And, a process that has to happen as reliably and stably as cell division also has to be flexible enough to allow the organism to grow and respond to its ever-changing environment. But little has been known about the molecular mechanics of how cells meet these challenges.

This work, done in collaboration with Kathleen Ryan and colleagues at the University of California, Berkeley, was supported by the NIH's National Institute for General Medical Sciences. Results appeared this week in an early online edition of Proceedings of the National Academy of Sciences.

Energy dependent proteases can be thought of as tiny molecular-level machines, says Chien. By selectively cutting and destroying key proteins at precise time points during cell division, they take charge of when, and at what rate, a cell grows and divides. They are found in all kingdoms of life, but are especially important in bacteria where they help cells overcome stressful conditions such as an attack by antibiotic treatment.

"When the environment becomes damaging, these proteases selectively target particular proteins to stop cell division so the bacteria can turn to focus instead on repair until the stress is over," Chien explains. "Understanding how bacteria use these machines at the cellular and molecular level could reveal avenues for discovery of new drugs to treat infectious diseases."