Circulatory zinc transport occurs at distinct interdomain sites on mammalian albumins

Zinc is an essential nutrient in the body that is required for virtually all biological processes, therefore its homeostasis and trafficking is of fundamental interest. Serum albumin is the major carrier of Zn²⁺ in the blood and is required for its systemic distribution. In collaboration with Prof. Wladek Minor (University of Virginia), Dr Maksymilian Chruszcz (University of South Carolina) and Dr Claudia Blindauer (University of Warwick), the Stewart lab present the first crystal structures of human serum albumin (HSA) and equine serum albumin (ESA) in complex with Zn²⁺. The structures allow unambiguous identification of the major zinc binding site on these two albumins, as well as several further, weaker zinc binding sites. Furthermore, analysis of Zn²⁺ binding to HSA and ESA proved the presence of secondary sites with 20-50-fold weaker affinities, which may be important under certain physiological conditions. Collectively, these findings are critical to our understanding of the role serum albumin plays in circulatory Zn²⁺ handling and cellular delivery. The new findings are published in the open-access journal, Chemical Science. Full text of the article is available here.