Molecular architecture and function of ZnT transporters

Zinc transporters (ZnT) form an important class of zinc efflux proteins in mammals. Nine ZnT transporters, designated ZnT1-ZnT8 and ZnT10, have been identified to date. Recent reports have established that the ZnT transporters are localized to various intracellular compartments and the plasma membrane. They play essential roles in multiple biological processes and are involved in zinc-related human diseases. The ZnT transporters function as Zn(2+)/H(+) exchangers. Based on the X-ray structures of and sequence homology to bacterial homologues, they are thought to form dimers possessing one essential zinc-binding site within the transmembrane domains of each monomer, and a binuclear zinc-sensing and binding site in the cytoplasmic C-terminal region. This chapter summarizes the molecular characteristics of ZnT transporters and reviews our current knowledge of their structure, biological functions, and regulation, with the emphasis on the most recent advances. Molecular characterization of the ZnT homologues of bacteria, yeast, plant and model organisms are also described, because they have contributed to the major advances in our understanding of the ZnT protein function.