Human Immunoglobulin G Fc hinge region (IgG Fc hinge)

The Human Immunoglobulin G (IgG) Fc hinge region is a flexible, proline-rich amino acid sequence that connects the antigen-binding (Fab) fragments to the crystallizable (Fc) region of the antibody (Vidarsson et al., 2014, PMID: 25368619). This region is essential for providing the segmental flexibility necessary for bivalent binding to antigens and for the proper orientation of the Fc domain to interact with effector molecules like C1q and Fc gamma receptors (Roux et al., 1997, PMID: 9334253). In the context of therapeutics, the hinge region is the specific target for the enzyme Imlifidase (IdeS), which cleaves IgG at this site to rapidly eliminate pathogenic antibodies in conditions like highly sensitized kidney transplantation (Jordan et al., 2017, PMID: 28767611). Additionally, the hinge region is frequently engineered in Fc-fusion proteins and therapeutic antibodies to modulate effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) (Strohl, 2009, PMID: 19807235). Its structural integrity is also vital for the interaction with the neonatal Fc receptor (FcRn), which governs the long serum half-life of IgG (Roopenian & Akilesh, 2007, PMID: 17848980). Consequently, the hinge region serves as both a structural scaffold for drug design and a direct target for enzymatic neutralization of autoantibodies. The hinge's susceptibility to proteolysis is also a key factor in the stability of therapeutic proteins during manufacturing and storage.

Other names

IgG hinge regionImmunoglobulin G hingeFc hinge domainIdeS cleavage site

Imlifidase (IdeS) is a cysteine protease that specifically cleaves the hinge region of human IgG, converting it into F(ab')2 and Fc fragments, thereby neutralizing its ability to trigger effector functions (Hansson et al., 2015, PMID: 25535376).