Metalloproteins: structure and function-X-ray structural studies of metal-binding to human serum transferrin: metal-induced conformational changes and biocoordination of metals

摘要

Human serum transferrin (hTf) is an indispensable serum protein primarily responsible for carrying ferric ions Fe(III) inside the human circulatory system [1]. Metal-induced conformational change of the protein is a momentous process for specific transferrin-receptor (TfR)-transferrin (hTf) recognition, leading to cellular uptake of ferric ions through a 'receptor-mediated endocytosis' [1]. It has been reported that hTF is capable of binding various multivalent metals such as Bi(III), Ga(III), In(III), Ru(III), Ti(IV), Yb(III), Dy(III), Pt(II), etc., and may play an critical role in delivery of metallodrugs [1,2]. In addition to the conventional bicarbonate, other anions such as oxalate and malonate, may serve as alternative synergistic anions to stabilize metal coordination [1]. However structural evidence of hTf binding to other metal ions and synergistic anions as well as the resulting conformational changes to hTf are still currently lacking.