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. 2015 Dec;26(12):746–757. doi: 10.1016/j.tem.2015.09.012

Figure 2.

Figure 2

Iron Regulatory Protein 1 (IRP1) Functions as Cytosolic Aconitase and RNA-Binding Protein (RBP). (A) IRP1 binds to several mRNAs when not assembled with the 4Fe–4S cluster due to low intracellular concentrations of iron. Among the best-studied examples is the binding of IRP1 to the iron-responsive element (IRE) in the 5′ untranslated region (UTR) of the ferritin mRNA to repress its translation. Since this mRNA encodes an iron-storage protein, diminished ferritin levels will promote an increase of free iron. Conversely, IRP1 increases the stability of transferrin receptor mRNA when binding to IREs in its 3′ UTR. An increase in transferrin receptor levels will promote cellular iron uptake. (B) Conversely, when IRP1 bears a 4Fe–4S cluster due to high intracellular iron concentration, it becomes active as cytosolic aconitase, catalyzing the interconversion between citrate and isocitrate. (C) Ribbon diagram of IRP1 bound to an IRE (PDB 3SNP). (D) Ribbon diagram of IRP1 crystalized as aconitase with the active site 4Fe–4S cluster (shown in red) (PDB 2B3Y).