Zinc transporters regulate subcellular zinc distributions to ensure proper metalation of a wide range of cellular proteins that amount to about one quarter of a mammalian proteome. For example, a human zinc transporter (ZnT8) enriches zinc in the insulin-containing vesicles of pancreatic beta cells where zinc is required for insulin dense core formation. The vesicular zinc is co-released with insulin in response to glucose stimulations, and serves as a feedback signal molecule that regulates insulin secretion and clearance. Our research is to understand which step in zinc transport may be modulated and how. The physicochemical principles governing zinc transport have been investigated using an integrated approach of membrane biochemistry, biophysics and structural biology. Parallel cell biology and proteomic approaches are used to understand how these physicochemical principles are applied to mammalian zinc transporters and integrated to physiology of pancreatic beta cells.
Visualizing the kinetic power stroke that drives proton-coupled Zn(II) transport. Nature (2014), in press.