Molecular Determinants of the Human Zinc Transporter, Hzip4

Abstract

Zinc is an essential micronutrient which is required for the function of hundreds of cellular enzymes. In addition, zinc is the second most abundant transition metal found in biological systems (iron is most abundant). However, the concentration of free zinc is nano to picomolar since most zinc is bound to proteins. This makes investigating the mechanism of zinc transport across the plasma membrane a challenge. Our interest has been to elucidate the mechanism of zinc transport mediated by one member of the ZIP family of proteins. To this end, we have developed a radiometric uptake assay to study the mechanism of zinc transport. In addition, we have expressed and purified specific domains of the protein to examine the role of these domains in zinc coordination and transport. Thus, using a mixture of biochemical and biophysical techniques, we have begun to describe the mechanism of zinc transport to gain insight into the function of this protein.