Zinc-mediated structural and functional regulation of ERp44 and ERGIC-53 in protein quality control

Zinc ions (Zn2+) are essential trace metal ions in the human body. Intracellular Zn2+ levels are tightly regulated by two metal transporter families: ZIPs, which mediate Zn2+ influx into the cytosol, and ZnTs, which export Zn2+ from the cytosol to the extracellular space or sequester it into the cellular organelles. Within cells, Zn2+ plays multiple roles, acting as a catalytic cofactor for numerous enzymes, stabilizing protein structures, and functioning as a second messenger in signal transduction. In addition, Zn2+ is involved in the transient regulation of enzymatic activities. Here, we review recent findings that reveal novel roles of Zn2+ in the structural and functional regulations of the molecular chaperone ERp44 and the cargo receptor ERGIC-53, both of which operate for protein quality control in the early secretory pathway.