When should we explicitly model the dimerization of a transcription factor with many states? NsrR as a case study

Marc R. Roussel

University of Lethbridge

"When should we explicitly model the dimerization of a transcription factor with many states? NsrR as a case study"

Creating models in which a protein has multiple states due to the binding of effectors or covalent modification is challenging. These challenges are multiplied when the protein dimerizes due to the combinatorial increase in the number of states of the assembly. In bacteria, NsrR controls the expression of genes associated with nitrogen oxide metabolism. The NsrR holoprotein holds an iron-sulfur cluster that reacts with nitric oxide (NO) in multiple steps, and typically acts as a repressor. The various nitrosylation states of NsrR are functionally important because binding to different gene promoters is differentially sensitive to the nitrosylation state of NsrR's iron-sulfur cluster. Moreover, the active form of NsrR is a dimer, leading to the combinatorial complexity mentioned above. Based on a model for the control of Hmp, an NO dioxygenase, by NsrR in emph{Streptomyces coelicolor}, conditions under which it may be possible to ignore the dimeric nature of a transcription factor or, conversely, conditions under which it would be prudent to consider transcription factor dimers explicitly, are studied.

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