A “bug” called Rhodospirillum rubrum has the unusual ability to dine on carbon monoxide, the odorless gas that’s lethal to animals.
The bacterium lives in freshwater lakes and ponds around the world, where it turns sunlight into energy just as algae do. But when there’s no light or oxygen around and R. rubrum senses carbon monoxide, it switches on a set of genes that allow it to grow by breaking down this poison.
In the October issue of Nature Structural Biology, a team of researchers from the University of California-Irvine and University of Wisconsin-Madison describe the structural details of CooA, the protein that senses carbon monoxide and turns on the genes for proteins that degrade it. The members of the research team included: Thomas Poulos, William Lanzilotta and David Schuller from UC-Irvine; and Gary Roberts, Marc Thorsteinsson, and Robert Kerby from the UW-Madison.
The study provides insights into the workings of proteins called transcription factors, which are found in all organisms. Transcription factors bind to specific regions of DNA and prompt cells to produce the proteins coded by that DNA.
According to Roberts, CooA is a model for studying a family of transcription factors called catabolite activator proteins (CAP). The family is named after CAP, the first such transcription factor discovered. CAP is among the best-understood examples of transcription factors in biology.
“Along with CooA, there are more than 60 similar bacterial transcription factors in the CAP family,” he says. “For example, one regulates how virulent a bacterium is. Another turns on genes needed to break down toxins.”
CooA also is a heme protein. Heme proteins perform essential functions in life by binding to and carrying things. For example, hemoglobin in blood transports oxygen throughout the body.
UW-Madison biochemists Robert Burris and Paul Ludden have studied R. rubrum for 30 years to understand how it fixes nitrogen. Their work led to a collaboration with Roberts and his colleagues in the Department of Bacteriology, who discovered CooA and the genes it regulates.
Crystallographer Thomas Poulos and his colleagues at UC-Irvine study how the structure of heme proteins explains how they work. When the California researchers became interested in CooA, the Wisconsin scientists from the College of Agricultural and Life Sciences joined them in the study.
The structure of CooA helps scientists understand how a molecule can act as a switch to turn genes on. Before these transcription factors switch from “off” to “on,” they must first bind to a specific molecule. That molecule triggers a change in their shape. For CooA, carbon monoxide triggers the change; for CAP it”s cyclic AMP. Scientists had already determined the structure of CAP in its “on” position — after it changed shape and was bound to DNA. The article in Nature Structural Biology describes the structure of CooA in the “off” position — before it changed shape and while it was incapable of binding DNA.
“By comparing the two very similar molecules in the ”off” and ”on” position, we now have a much better idea of how these proteins change their shape, exposing areas that then bind to specific DNA regions. This is an important model for how this whole family of transcription factors operates to produce specific sets of proteins in bacteria,” Roberts says.
He believes the results also will help researchers understand the properties of heme proteins and how they work. The UW-Madison team has already identified mutant forms of CooA with very different responses to carbon monoxide. Some of the mutant forms switch to the “on” position in response to small molecules other than carbon monoxide.
The UW-Madison portion of the research was supported by state funding to the College of Agricultural and Life Sciences, and a grant from the National Institutes of Health (NIH).