HOUSTON (May 5, 2013)- A small regulatory protein that controls iron-sulfur cluster production in E. coli can do more than simply turn off the genes involved in making the clusters -- it can also turn off the production of genes that use the iron-sulfur clusters. This is unusually complicated behavior for a bacterial repressor, and a first among metallocluster-binding transcription regulators, say a group of scientists led by Kevin Phillips, Ph.D., from The Methodist Hospital Research Institute and Patricia Kiley, Ph.D., from the University of Wisconsin-Madison, in the most recent Nature Structural & Molecular Biology.
The regulatory protein is IscR, which can bind iron-sulfur clusters, altering the protein's behavior. With iron-sulfur attached, a IscR dimer binds to the regulatory sequence upstream of genes that control iron-sulfur cluster production, turning off transcription -- a classic negative feedback relationship. As iron-sulfur builds up inside the cell, more of the IscR will be found with iron-sulfur clusters attached, stymieing the production of more iron-sulfur clusters, which can be toxic in excess.
Without iron-sulfur around, however, IscR doesn't necessarily float idly about, say Phillips, Kiley, and their coauthors. If the E. coli cell requires more iron-sulfur clusters and has the materials to make them, IscR will not interfere. But if the cell is simply incapable of producing or maintaining iron-sulfur clusters, IscR will bind to other regulatory segments of the bacterial genome that control production of genes that would use iron-sulfur clusters, turning those genes off and, possibly, saving the cell from wasting precious energy.
"We paint a picture of how such a small and simple protein could display this complex regulatory behavior that we typically equate with bigger multiprotein complexes," said Phillips, assistant member of the Diabetes & Metabolic Disease Program at TMHRI.
Also contributing to this work were Senapathy Reajagopalan (TMHRI), Sarah Teter (University of Houston), Petrus Zwart (Lawrence Berkeley National Laboratory), and Richard Brennan (Duke University School of Medicine). It was funded by grants from the NIH and The Methodist Hospital Research Institute.