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 alpha 1 and alpha 2 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 CH2 and CH3 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.
Division of Biology 156-29, California Institute of Technology, Pasadena 91125.
W P
WP
Burmeister
A H
AH
Huber
P J
PJ
Bjorkman
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D003196:Computer Graphics; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D051381:Rats; D011961:Receptors, Fc / Q000737:chemistry* / Q000378:metabolism
D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc