ApoIscR

apoIscR is the apoprotein form of IscR, a transcriptional regulator that monitors iron–sulfur (Fe–S) cluster status in many bacteria. IscR can exist as holoIscR, in which an Fe–S cluster is coordinated within the protein, or as apoIscR, which lacks the cluster. The presence or absence of the Fe–S cluster alters IscR’s DNA-binding properties and promoter specificity, enabling the cell to adjust gene expression in response to Fe–S cluster biosynthesis and cellular iron status.

Structural and binding features: IscR functions as a dimer with an N-terminal DNA-binding domain and a C-terminal region that coordinates the Fe–S cluster in the holo form through conserved cysteine ligands. HoloIscR preferentially binds to promoter sites associated with the isc operon and related Fe–S cluster machinery, whereas apoIscR recognizes a distinct set of promoters (often referred to as type-2 sites) and can regulate different targets. The apo form thus acts as a sensor that shifts regulatory output when the Fe–S cluster is damaged, lost, or not assembled.

Regulatory role and physiological relevance: IscR coordinates the expression of Fe–S cluster assembly pathways, including the isc operon and, in some bacteria, the suf operon or oxidative stress response genes. ApoIscR accumulation under conditions of Fe–S cluster deficiency or oxidative stress tends to reprogram transcription to bolster Fe–S maintenance and stress adaptation, while holoIscR reflects a state of cluster abundance. As a member of the Rrf2 family, apoIscR contributes to the broader network that maintains Fe–S homeostasis and iron metabolism in bacteria.