Structural and Biochemical Characterization of Silver/Copper Binding by Ferritin.

Ferritin with a highly symmetrical cage-like structure is not only key in the reversible storage of iron in efficient ferroxidase activity; it also provides unique coordination environments for the conjugation of heavy metal ions other than those associated with iron. However, research regarding the effect of these bound heavy metal ions on ferritin is scarce. In the present study, we prepared a marine invertebrate ferritin from (DzFer) and found that it could withstand extreme pH fluctuation. We then demonstrated its capacity to interact with Ag or Cu ions using various biochemical and spectroscopic methods and X-ray crystallography. Structural and biochemical analyses revealed that both Ag and Cu were able to bind to the DzFer cage via metal-coordination bonds and that their binding sites were mainly located inside the three-fold channel of DzFer. Furthermore, Ag was shown to have a higher selectivity for sulfur-containing amino acid residues and appeared to bind preferentially at the ferroxidase site of DzFer as compared with Cu. Thus, it is far more likely to inhibit the ferroxidase activity of DzFer. The results provide new insights into the effect of heavy metal ions on the iron-binding capacity of a marine invertebrate ferritin.