A research team led by scientist David Liberter from the Autonomous University of Barcelona (UAB) has identified a molecular mechanism that regulates cell division in bacteria. The findings reveal how the MraZ protein binds to the dcw gene cluster to control this process. The survey results are nature communications.
Cell division is essential for all living organisms and depends on the coordinated activity of many proteins and regulatory components. In most bacteria, the instructions for this process are organized within a group of genes known as the dcw operon. This cluster contains the genetic information needed to produce proteins involved in both cell division and the construction of bacterial cell walls.
How the dcw operon activates cell division genes
The genes in this cluster are turned on by proteins known as transcription factors. These proteins bind to specific parts of DNA called promoters, which indicate where transcription begins. This starting point appears just before the first codon (the basic unit of genetic information), which marks the beginning of the protein sequence.
One of these transcription factors is MraZ, which is also the first gene in the dcw operon of all bacteria. When MraZ activates the operon, the genes in the cluster produce proteins necessary for bacterial division. Thus, MraZ acts as a key regulator controlling the activity of operons that control cell division in most bacterial species.
Imaging the molecular mechanisms of bacterial division
The UAB research group, led by David Liberter, a full professor in the Department of Biochemistry and Molecular Biology and a research associate in the UAB Institute of Bioengineering and Biomedical Sciences (IBB-UAB), has uncovered the detailed mechanisms behind this regulation. The research team used advanced structural biology techniques such as X-ray crystallography and cryo-electron microscopy.
These techniques allowed scientists to determine how the MraZ transcription factor binds to the promoter of the dcw operon in bacteria. Mycoplasma genitalium. This microorganism is frequently used in laboratory research because it has a very small genome.
Atomic level view of MraZ protein binding DNA
The promoter region of the dcw operon contains four repetitive segments, or “boxes,” each consisting of six nucleotides. These repeated DNA sequences play an important role in regulating transcription.
By examining the system with cryo-electron microscopy, the researchers were able to observe interactions between the MraZ protein and the DNA bases of these four repeat boxes at near-atomic resolution. Their observations showed that MraZ must undergo a conformational change in order to successfully bind to the operon.
“This is a surprising observation. The MraZ protein is an octamer formed by eight identical subunits bound in the shape of a donut, but its curvature would never allow it to bind to the four ‘boxes’ of the promoter. However, we see how the donut breaks and deforms so that four of the subunits can bind to the four boxes of the promoter to control cell division,” explains David Liberter.
Major advances in understanding bacterial cell division
Directly visualizing how MraZ interacts with promoter DNA that initiates cell division would be a major advance. Until now, researchers studying this system have relied primarily on biochemical experiments and computer modeling to deduce how its mechanisms work.
Reverter said the control systems identified in this study are likely widespread among bacteria. “This is universal in most bacteria, as all MraZ proteins are very similar, have the same octameric structure, and have similar DNA sequences in the promoters of the operons that regulate cell division,” Liberter concludes.
International cooperation behind the research
The research was led by a team led by David Liberter from the Biotechnology and Biomedical Research Institute and UAB’s Department of Biochemistry and Molecular Biology. This research was carried out in collaboration with the ALBA synchrotron and cryo-electron microscopy service at the Institute of Genetics and Molecular and Cell Biology in Strasbourg, France.
