Logan Research: Metal Activated Repressors
Three dimensional structure of IdeR, the iron-dependent regulator, from Mycobacterium tuberculosis.
This work is supported by NIH AI021628 with John R. Murphy, Boston University.
Upon entering a host organism, pathogenic bacteria become iron starved. This triggers a virulence response, resulting in the synthesis and secretion of toxic protein factors that kill neighboring host cells. The virulence response is generally accompanied by the synthesis and release of iron scavenging and transport proteins, allowing the bacterium to replenish its iron stores and function normally.
In many bacteria, iron levels are sensed by proteins of the diphtheria toxin repressor (DtxR) family. In Mycobacterium tuberculosis, the DtxR homologue is IdeR, the iron-dependent regulator (shown on the left). Iron sensing via IdeR is crucial for the survival of M. tuberculosis - deletion mutants are lethal. Furthermore, over-expression of a hyperactive single-site mutant of IdeR are avirulent, in other words, a single-site mutation in IdeR renders M. tuberculosis incapable of mounting a virulence response under low iron conditions.
I want to understand how iron binding regulates repressor activity in IdeR and related proteins. In the future, we hope to use this information to further define the virulence response in these bacteria, and maybe develop novel therapeutic approaches to treating tuberculosis.
Students working on this project learn a variety of techniques to support their research. You will receive basic training in current molecular biology and protein chemistry techniques. In addition, you will learn to combine structural information with biophysical data to reveal important aspects of how biological activity in these proteins is regulated by iron.
For more information, see our recent publications:
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