Figure 1.

TfR-mediated intracellular iron uptake. a. Once bound to two Fe³⁺ ions, the complex Fe₂Tf is recognized by the TfR membrane receptor and internalized via endocytosis; metal release occurs at endosomal pH. This is the proposed pathway for intracellular uptake of exogenous metals such as Cm³⁺. b. Metal binding site of the Tf N-Lobe, with Tyr 188, Tyr 95, His 249, Asp 63 and a synergistic carbonate anion participating in the coordination of Fe³⁺.¹⁴ c. Structure of the (Tf)₂-TfR complex, with TfR in green, Tf N-lobes in red) and Tf C-lobes in blue, adapted from previously reported X-ray data.¹⁵