Immunoglobulin G Fc region dimeric interface (CH3-CH3 interface)

The Fc domain-mediated dimeric interface is the structural region, primarily within the CH3 domains of the immunoglobulin G (IgG) heavy chains, that facilitates the non-covalent assembly of two heavy chains into a stable homodimer. This interface is defined by a network of hydrophobic interactions and conserved salt bridges, such as the K409-D399 pair, which are essential for the integrity and effector functions of the antibody [2, 6]. In the pharmaceutical industry, this interface is a primary target for engineering bispecific antibodies, utilizing 'knobs-into-holes' and other heterodimerization technologies to ensure correct chain pairing [4, 14]. Additionally, the interface serves as a therapeutic target in autoimmune diseases like neuromyelitis optica (NMO), where blocking the Fc-mediated clustering (hexamerization) of autoantibodies can prevent the overactivation of the complement system and subsequent tissue damage [9, 11]. Experimental inhibitors, including small peptides and bacterial proteins like Staphylococcal protein A, demonstrate the potential of targeting this site to modulate immune responses and improve the safety profiles of therapeutic proteins [10, 13].

Other names

Fc domain-mediated dimeric interfaceCH3-CH3 interfaceFc dimerization interfaceFc-Fc interfaceIgG Fc dimer interface

Disruption of the CH3-CH3 homodimeric interface to prevent pathogenic antibody clustering (hexamerization) or to enable the assembly of multispecific antibody formats.