Molecular map provides clues to zinc-related diseases

Molecular map provides clues to zinc-related diseases

Mapping the molecular structure where medicine goes to work is a crucial step toward drug discovery against deadly diseases.

Researchers at Michigan State University have taken that critical first step by providing a crystal structure of the extracellular domain, or ECD, of ZIP4 - the exclusive protein responsible for the uptake of zinc from food. The ZIP family consists of thousands of zinc/iron transporter proteins, and this work represents the first-ever structural information of the ZIP family at the atomic level.

The results are published in the journal Nature Communications and provide a roadmap for potential target sites for people suffering from acrodermitis enteropathica, a rare but lethal genetic disorder leading to severe zinc deficiency, and pancreatic cancer where ZIP4 is abnormally overexpressed.

"Many drug candidates fail during development because their targets are buried inside the cell," said the lead suthor. "With ZIP4, though, the large ECD is fully exposed to the extracellular space and quite accessible."

Author revealed that ZIP4-ECD acts as a critical accessory domain that is essential for optimal zinc transport. Therefore, targeting it appears to be a promising strategy regulating the function of ZIP4.

The study also revealed that many human ZIP proteins share a common architecture in their ECDs. This sheds light on structural and functional studies of other ZIP proteins involved in a variety of cancers, osteoarthritis and other serious diseases.