PMC:7228307 / 34394-35230
Annnotations
Crystallographic analyses of the human IgG1‐Fc complexed with FcγRI, FcγRII or FcγRIII show that these interactions are similar in topology, and asymmetric in nature. The second extracellular domain of the FcγR inserts between the two heavy chains. Here it makes contacts with the lower hinge of both H chains and with residues of the adjacent BC loop of one CH2 domain and the FG loop of the other. The N‐linked glycan at asparagine 297 (N297) of the heavy chain is essential for the structural integrity of the IgG‐Fc by affecting the spacing and conformation of the CH2 domains. Indeed, its removal ablates FcγR binding.67 Of particular relevance to therapeutic mAb development is that the normal low‐affinity IgG interaction with FcγRIIIa is profoundly increased by the removal of the core fucose from the N297 Fc oligosaccharide.68