Immunoglobulin G conserved lower hinge region (IgG lower hinge)

The conserved lower hinge region of Immunoglobulin G (IgG) is a pivotal structural motif located between the CH1 and CH2 domains of the antibody heavy chain (UniProt: P01857). This region, typically spanning residues 233 to 239 (EU numbering), is essential for mediating the effector functions of the immune system, as it facilitates the binding of IgG to Fc gamma receptors (FcγRs) on immune cells and the C1q protein of the complement system (PubMed: 27535424). By enabling these interactions, the lower hinge region allows IgG to trigger processes such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (StatPearls: Immunoglobulins). In the context of disease, this region is a target for therapeutic intervention in conditions driven by pathogenic IgG, such as autoimmune disorders and organ transplant rejection (PubMed: 30046015). Drugs like Imlifidase (IdeS) are designed to specifically cleave the IgG molecule at this conserved hinge site, effectively neutralizing the antibody's ability to cause tissue damage while leaving the Fab fragments intact but disconnected from the Fc-mediated inflammatory machinery (Hansa Biopharma). This targeted cleavage results in a rapid reduction of functional IgG levels, providing a therapeutic window for medical procedures like desensitization in kidney transplantation.

Other names

IgG lower hinge regionFc gamma receptor binding siteC1q binding siteIdeS cleavage siteLower hinge of Immunoglobulin G

Proteolytic cleavage of the IgG heavy chain at the lower hinge region (specifically between Gly236 and Gly237 in IgG1), which separates the Fab fragments from the Fc region, thereby abolishing effector functions such as Fc receptor binding and complement activation (PubMed: 27535424).