We've updated our Privacy Policy to make it clearer how we use your personal data.

We use cookies to provide you with a better experience. You can read our Cookie Policy here.

Unpacking the Mysteries of Bacterial Cell Cycle Regulation

Unpacking the Mysteries of Bacterial Cell Cycle Regulation

Unpacking the Mysteries of Bacterial Cell Cycle Regulation

Unpacking the Mysteries of Bacterial Cell Cycle Regulation

Read time:

Want a FREE PDF version of This News Story?

Complete the form below and we will email you a PDF version of "Unpacking the Mysteries of Bacterial Cell Cycle Regulation"

First Name*
Last Name*
Email Address*
Company Type*
Job Function*
Would you like to receive further email communication from Technology Networks?

Technology Networks Ltd. needs the contact information you provide to us to contact you about our products and services. You may unsubscribe from these communications at any time. For information on how to unsubscribe, as well as our privacy practices and commitment to protecting your privacy, check out our Privacy Policy

Joanne Lau, a microbiology doctoral student, and her advisor Peter Chien in the Biochemistry and Molecular Biology Dept. at UMass Amherst, report how two molecular pathways, protein degradation and phosphorylation, work together to ensure normal bacterial growth, in a recent early online edition of Molecular Cell. Chien says that because controlled protein degradation is critical for bacterial virulence, "this work introduces new pathways for us to target in the discovery of sorely needed new antibiotics."

In bacteria, the cell cycle is very tightly controlled by protein-digesting enzymes called proteases that selectively destroy other proteins, called substrates, at appropriate times while the cell is undergoing growth and division. At the same time, another process called phosphorylation chemically modifies different proteins to regulate their activity in a cell-cycle-dependent way, Chien explains.

Although the energy-dependent proteases that carry out most protein degradation can directly recognize some substrates, biological regulation often requires additional factors known as adaptors to be present to "tune" substrate selection more precisely. In the bacterium Caulobacter crescentus studied in the Chien lab, one of these adaptors, a small protein called CpdR, is specifically phosphorylated at different times in the cell cycle. Previous studies had shown that the timing of this phosphorylation correlated with the degradation of many proteins by a protease called ClpXP.

Chien says, "Before this work, we thought most adaptors were binding to the protease and substrate at the same time, effectively leashing them together to force them to interact. Surprisingly, Joanne found that CpdR bound principally to the ClpXP protease, but didn't seem to bind the substrate well at all. Instead, CpdR binding to the ClpXP protease prepared, or primed, the protease for engaging substrates. This primed protease was now also able to recruit additional adaptors that could deliver even more protease substrates."

He adds, "By not specifically interacting with any single substrate, this new mechanism of protease priming allows for surprisingly broad recognition of both substrates and additional regulators. This mechanism lets the cell control multiple pathways with a single regulator, which is useful when bacteria have to respond rapidly, such as during the stress they undergo when treated with antibiotics. However, this could also lead to unwanted degradation of off-target proteins. Understanding this balance of specificity and broad recognition is an outstanding question."

Chien and Lau say the "fascinating mystery" at the heart of this work has been to figure out how the cell cycle, made up of the many events that happen when cells divide, are so precisely coordinated by CpdR and other factors. The researchers say their new understanding of how adaptors work could answer the question of how a single regulator like CpdR could globally control degradation by a protease, ClpXP.