The formation and Zn²⁺-dependence of histidine-rich glycoprotein-containing immune complexes.

Histidine-rich glycoprotein (HRG) is a plasma adapter protein that participates in a range of hematological processes, including the regulation of immune function. HRG is known to participate in the formation of complexes with complement factors within both the “classical” and “alternative” pathways, and with antibodies, Fc receptors and membrane attack complex components. Many of these interactions are regulated allosterically by the binding of Zn²⁺ ions to a region of HRG known as the histidine-rich region (HRR). Zinc is an essential micronutrient in humans and other mammals; zinc deficiencies, which are relatively widespread, are known to impact greatly upon the immune system. In this section we will review the role that HRG plays in the formation of immune protein complexes and given the known importance of Zn²⁺ status in maintaining a healthy immune system, discuss the various contributions that this metal ion may play in regulating HRG complex formation.