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 to class I major histocompatibility complex (MHC) molecules, despite differences in the ligands they bind (the Fc portion of IgG and antigenic peptides, respectively). A low-resolution crystal structure of the complex between FcRn and Fc localizes the binding site for Fc to the side of FcRn, distinct from the tops of the αl and α2 domains which serve as the peptide and T-cell receptor binding sites in class I molecules. FcRn binds to Fc at the interface between the Fc C_H2 and C_H3 domains, which contains several histidine residues that could account for the sharply pH-dependent FcRn/IgG interaction. A dimer of FcRn heterodimers observed in the co-crystals and in the crystals of FcRn alone could be involved in binding Fc, correlating with the 2:1 binding stoichiometry between FcRn and IgG (ref. 4) and suggesting an unusual orientation of FcRn on the membrane.
© 1994 Nature Publishing Group. Received 29 June; Accepted 6 October 1994. We thank D. Sabatini for suggesting that networks of complexes could exist between adjacent microvilli; D. Vaughn for help with data collection; the staff at CHESS; and M. Raghavan, L Gastinel and N. Simister for critical reading of the manuscript. Coordinates will be deposited in the Brookhaven databank and can be requested by e-mail (email@example.com). This work was supported by the Howard Hughes Medical Institute (P.J.B.) and an EMBO fellowship (W.P.B.). A.H.H. was supported by a Howard Hughes Predoctoral Fellowship.