CRYSTAL-STRUCTURE OF THE COMPLEX OF RAT NEONATAL FC RECEPTOR WITH FC

THE neonatal Fc receptor (FcRn) transports maternal immunoglobulin G ( IgG) to the bloodstream of the newborn. FcRn is structurally similar t o class I major histocompatibility complex (MHC) molecules(1,2), despi te differences in the ligands they bind (the Fc portion of IgG and ant igenic peptides, respectively). A low-resolution crystal structure of the complex between FcRn and Fc localizes the binding site for Fc to t he side of FcRn, distinct from the tops of the alpha 1 and alpha 2 dom ains which serve as the peptide and T-cell receptor binding sites in c lass I molecules. FcRn binds to Fc at the interface between the Fc C(H )2 and C(H)3 domains, which contains several histidine residues that c ould account for the sharply pH-dependent FcRn/IgG interaction(3). A d imer of FcRn heterodimers observed in the co-crystals and in the cryst als of FcRn alone(2) could be involved in binding Fc, correlating with the 2:1 binding stoichiometry between FcRn and IgG (ref. 4) and sugge sting an unusual orientation of FcRn on the membrane.